Next Article in Journal
Trust-Based Decision-Making in the Health Context Discriminates Biological Risk Profiles in Type 1 Diabetes
Next Article in Special Issue
Renal Tubular CD24 Upregulation Aggravates Folic Acid Induced Acute Kidney Injury: A Possible Role for T Regulatory Cells Inhibition in Mice
Previous Article in Journal
SARS-CoV-2 Infection (COVID-19) and Rhinologic Manifestation: Narrative Review
Previous Article in Special Issue
Predictors of the CD24/CD11b Biomarker among Healthy Subjects
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JPM
Volume 12
Issue 8
10.3390/jpm12081235
jpm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

CD24: A Novel Target for Cancer Immunotherapy

by
Emmanouil Panagiotou
,
Nikolaos K. Syrigos
,
Andriani Charpidou
,
Elias Kotteas
and
Ioannis A. Vathiotis
*
Section of Medical Oncology, Third Department of Internal Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2022, 12(8), 1235; https://doi.org/10.3390/jpm12081235
Submission received: 4 July 2022 / Revised: 25 July 2022 / Accepted: 26 July 2022 / Published: 28 July 2022
(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)
Versions Notes

Abstract

:
Cluster of differentiation 24 (CD24) is a small, highly glycosylated cell adhesion protein that is normally expressed by immune as well as epithelial, neural, and muscle cells. Tumor CD24 expression has been linked with alterations in several oncogenic signaling pathways. In addition, the CD24/Siglec-10 interaction has been implicated in tumor immune evasion, inhibiting macrophage-mediated phagocytosis as well as natural killer (NK) cell cytotoxicity. CD24 blockade has shown promising results in preclinical studies. Although there are limited data on efficacy, monoclonal antibodies against CD24 have demonstrated clinical safety and tolerability in two clinical trials. Other treatment modalities evaluated in the preclinical setting include antibody–drug conjugates and chimeric antigen receptor (CAR) T cell therapy. In this review, we summarize current evidence and future perspectives on CD24 as a potential target for cancer immunotherapy.

1. Introduction

Checkpoint immunotherapy with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors has altered the treatment landscape in medical oncology, thus improving patient outcomes [1,2]. Additional immune checkpoint molecules that facilitate tumor immune evasion represent potential targets for novel immunotherapy strategies [3].
Cluster of differentiation 24 (CD24), also known as heat-stable antigen (HSA), is a highly glycosylated 31–34 amino acid protein attached to the cell surface by a glycosylphosphatidylinositol anchor [4]. It is normally expressed on B and T lymphocytes, monocytes, and granulocytes [4,5] as well as epithelial, neural, and muscle cells [5]. CD24 represents a costimulatory molecule for CD4+ T cell proliferation [6]. It has been shown to have a proapoptotic role in B cell precursors as well as in differentiated B cells, possibly through the activation of the MAPK pathway [7,8]; CD24 is a marker for B10 regulatory B cells, which restrain the immune response by regulating T cell activity [9]. In addition, CD24 is highly expressed in regulatory T cells and may regulate their immunosuppressive activity [10]. It is also involved in the differentiation of CD8+ T cells [11]. Thus, decreased CD24 expression may lead to uncontrolled T cell proliferation, with implications in autoimmunity [12]. Furthermore, CD24 interaction with P-selectin [13] mediates leukocyte binding to endothelial cells and activated platelets [14], therefore promoting cell migration [15]. CD24 also regulates the activity of several other adhesion molecules, including integrins, by affecting their localization in the cell membrane, possibly by activating Src-related kinases [15,16]. While it is also involved in the differentiation of neural stem cells [17], CD24 is transiently expressed during the development of the human central nervous system [18,19]. As a matter of fact, the activity of L1CAM (CD171), a neural signal transduction molecule which regulates neurite outgrowth, appears to be dependent upon its interaction with CD24-associated sialic acids [20].
CD24 also plays an important role in tumorigenesis. Surface CD24 expression in tumor cells has been linked with alterations in multiple oncogenic signaling pathways, including Src/STAT3 [21], EGFR [22], HER2 [23], Ras-like GTPase [24], MAPK [25,26], AKT/mTOR [27], WNT/β-catenin [28], and miRNA-related pathways [25]. Moreover, the cytoplasmic accumulation of CD24 may be involved in tumor cell proliferation, including p53 inactivation [4]. In this regard, the overexpression of CD24 has been documented in several malignancies, including breast [29,30], lung [31], colorectal [32], hepatocellular [27], pancreatic [33], ovarian [30], urothelial [34], prostate [35], and head and neck cancer [36], as well as in primary central nervous system (CNS) tumors [37,38] and hematologic malignancies [39,40,41] (Table 1).
Notably, the expression of CD24 in solid tumors has been correlated with worse prognosis, including the presence of more aggressive features and their metastatic spread in vivo [44]; in fact, CD24 expression has been shown to promote tumor growth and malignant behavior in a dose-dependent manner [45]. Tumor cell CD24 interaction with P-selectin on endothelial cells may account for the latter [4,46]. Additional mechanisms that depend upon the expression of CD24 and are implicated in tumor cell extravasation and metastasis include rolling on E-selectin [47] and binding to fibronectin in the extracellular matrix [47]. CD24 represents a target of the transcription factor hypoxia inducible factor-1α (HIF-1α), a molecule commonly upregulated in hypoxic conditions, including during primary tumor growth and metastasis [48]. Intriguingly, metastatic tumor growth has been shown to be inhibited when CD24 activity is suppressed [34]. Finally, the surface expression of CD24 in peripheral blood leukocytes has been shown to be both sensitive and specific for the detection of colorectal adenoma and cancer in individuals undergoing colonoscopy [49]. Combined with peripheral blood CD11b expression, surface CD24 has also been evaluated as a potential screening tool for the detection of hematologic malignancies [50].
Its multifaceted role in both the regulation of the immune response and tumorigenesis has made CD24 a compelling target for the immunotherapy of cancer. In this review, we sought to summarize the available data on the role of CD24 in chemoresistance and antitumor immunity. In addition, we present clinical trials that have assessed the efficacy of CD24 blockade in cancer, either alone or in combination with other treatment modalities.

2. Resistance to Chemotherapy

In the preclinical setting, the overexpression of CD24 has been associated with resistance to several chemotherapy agents. Leukemia stem cells with CD24 surface expression appear to be resistant to doxorubicin, possibly through the activation of the Wnt/β-catenin and PI3K/Akt pathways [51]. Likewise, downstream activation of the PI3K/Akt pathway by CD24 has been shown to reduce the sensitivity of retinoblastoma cells to vincristine [52]. Thus, the inhibition of autophagy through the PI3K/Akt pathway seems to be involved in the development of CD24-mediated chemoresistance [53]. Another mechanism of resistance may involve the activation of MAPK-related pathways, resulting in temporary inhibition of cell proliferation [54]. CD24 may also enhance cytotoxicity from DNA-damaging agents through the disruption of NF-κB signaling [55]. CD24+ head and neck squamous cell carcinoma (HNSCC) cell lines were resistant to cisplatin, and this effect was reversed by CD24 inhibition [56]. Additional preclinical data support chemoresistance to doxorubicin and cisplatin for CD24+ ovarian cancer [57] and to gemcitabine for CD24+ pancreatic cancer cell lines [58]. Moreover, the overexpression of CD24 has been linked with worse outcomes following chemoradiotherapy in patients with glioblastoma [59] and locally advanced HNSCC [36].
CD24-induced chemoresistance may be tissue-dependent. The induced expression of CD24 in endometrial cell lines increased resistance to doxorubicin and paclitaxel [60]. Furthermore, treatment with anti-CD24 antibodies conferred increased sensitivity to multiple chemotherapy agents in colorectal cancer models. However, this is not the case for early breast cancer, where the increased expression of CD24 has demonstrated conflicting results across studies [61,62]. The latter may be due to polymorphisms in the CD24 gene, which may be culpable of discordances in tumor immune infiltration and thus explain the differences in the pathologic response to neoadjuvant chemotherapy [63].
Finally, the overexpression of CD24 has been linked with resistance to targeted therapies. In melanoma, the increased expression of CD24 was associated with resistance to BRAF inhibitors [64]. In addition, CD24 was shown to promote resistance to sorafenib in hepatocellular carcinoma [27]. CD24 was also shown be upregulated and to promote resistance to EGFR inhibition in lung adenocarcinoma cells resistant to gefitinib [65,66]. In addition, CD24 polymorphisms were associated with differences in survival outcomes after neoadjuvant treatment, which included bevacizumab in resected metastatic colorectal cancer [67].

3. Implications in Antitumor Immunity

Siglecs, or sialic-acid-binding immunoglobulin-like lectins, are a family of surface receptors that are expressed by immune cells and bind sialic acid-containing glycans, also known as sialoglycans [68]. Siglecs have been implicated in various components of the immune response, such as in the regulation of immune cell proliferation, survival, T cell and eosinophil activity, antigen presentation, and endocytosis signaling [69]. CD24 is the main ligand for Siglec-10 [30]; Siglec-10 is widely expressed by B cells, activated T cells, and monocytes [28]. The CD24/Siglec-10 complex engages danger-associated molecular pattern (DAMP) molecules, released as a result of tissue injury, in order to initiate a signaling cascade that is mediated by SHP-1 and/or SHP-2 phosphatases associated with the two immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic tail of Siglec-10. This inhibits TLR-mediated inflammation, which ultimately leads to the suppression of the immune response following tissue damage [70,71]. Selective interaction with DAMPs but not with pathogen-associated molecular pattern molecules (PAMPs), which are related to the recognition of “non-self” patterns associated with infection, provides the biologic basis for a differential response between healthy and neoplastic tissue as a result of CD24 blockade [71,72]. As a matter of fact, inactivating CD24 alterations may confer protection against autoimmune diseases such as systemic lupus erythematosus and multiple sclerosis [73]. The anti-inflammatory effects of CD24 activation have also been explored as a strategy to counteract immune-related adverse events (NCT04552704, NCT04060407), graft-versus-host disease [74], and as of late, COVID-19 [75]. The effects of CD24 signaling on immune cell activity are summarized in Table 2.
Several malignancies have been found to overexpress sialyated glycans, which connect with Siglec-10 and employ the CD24/Siglec-10 interaction as a means of tumor immune evasion [76]. This mimics the innate “recognition of self” signal that is emitted by injured tissues to inhibit inflammation and allow for tissue healing [76]. Aberrant sialyation has been linked with uncontrolled cell proliferation and malignant potential, as well as tumor immune evasion [77]. Mouse sepsis models have provided a possible mechanism for the inhibition of the CD24/Siglec-10 interaction and the resulting immunosuppression through the disruption of CD24 sialyation with the use of recombinant bacterial sialidases; however, this strategy harbors the risk of increasing susceptibility to sepsis secondary to bacterial infection [78].
In addition, the surface expression of CD24 has been described as a “do not eat me” signal, inhibiting phagocytosis by infiltrating Siglec-10-expressing macrophages [30]. In contrast, the loss of CD24 expression has been shown to increase phagocytosis by macrophages expressing Siglec-10 in renal clear cell carcinoma [79]. Furthermore, a decrease in Siglec binding to surface sialic acids promotes macrophage-mediated phagocytosis [80]. Silencing NPM/B23, a protein that induces CD24 expression, promotes macrophage-mediated phagocytosis by downregulating CD24, while the restoration of CD24 expression inhibits phagocytosis and therefore promotes immune evasion [81].
Natural killer (NK) cells have been shown to selectively eradicate less differentiated cells such as CD24+ ovarian cancer cells [57] and cancer stem cells [82]. This antitumor effect is largely dependent on the activation of the Natural Killer Group 2D (NKG2D) receptor [82]. NKG2D-mediated NK cell cytotoxicity has been correlated with intracellular reactive oxygen species (ROS) formation, with cells that have low ROS levels being more sensitive to NK cell-mediated killing [83]. The CD24/Siglec-10 interaction has been linked with NK cell dysfunction in hepatocellular carcinoma and could provide another pathway for CD24-mediated immune evasion [84].
The correlation between CD24 and PD-1/PD-L1 immune checkpoints has not been clearly established at this point. The overexpression of PD-L1 seems to downregulate surface CD24 in breast cancer cells [85]. Moreover, high PD-1 expression was correlated with decreased CD24 expression in B cells infiltrating hepatocellular carcinoma tumors, which resulted in decreased cytokine production [86]. Furthermore, treatment with CD24Fc reduced infiltration by PD-1-expressing T cells in vivo [87]. However, this was not the case in patients with NSCLC [88]. Although early indications for the interaction between CD24 and PD-(L)1 point towards tumor type specificity, more data are needed to draw definitive conclusions.
CD44 is a cell surface glycoprotein that acts as an adhesion molecule by binding to hyaluronic acid [89]. It is normally expressed on all hematopoietic as well as most epithelial cells [90]. While its possible role in tumorigenesis is currently under investigation, CD44 is widely used as a marker of cancer stem cells [91]. By regulating P- and L-selectin activity, CD44 is thought to be involved in hematogenous dissemination, including leukocyte recruitment and metastatic tumor spread [92]. More specifically, it appears to control tumor infiltration by the intratumoral movement of cytotoxic T cells [93] and may exert an immune suppressive effect upon its interaction with osteopontin [94,95]. Intratumoral movement is also regulated by the CD44/hyaluronic acid interaction, which is involved in the reorganization of the cytoskeleton that is necessary for cell migration [89]. CD44+/CD24–/low cells have been described as breast [96] and prostate cancer [97] stem cells; stem-like properties, including increased proliferation [96], angiogenesis [98], and resistance to chemotherapy [99], have been attributed to CD44+/CD24–/low NSCLC [100], and ovarian cancer cells as well [101]. However, the loss of CD24 expression does not appear to be necessary for cancer stemness. As a matter of fact, CD44+/CD24+ pancreatic cancer cells that express epithelial-specific antigens appear to possess several stem-like properties that have led them to be considered as tumor-initiating cells [102]. Targeting those cells in particular resulted in significant antitumor activity in vivo and could evolve into a potential strategy for pancreatic cancer immunotherapy [103]. Furthermore, CD44+/CD24+ melanoma cells have been shown to have greater tumor-forming potential in vivo than CD44+/CD24–, suggesting that the increased malignant potential might be attributable to CD24 expression [104].

4. CD24 Inhibition in Solid Tumors

4.1. Preclinical Data

Treatment strategies that have employed the inhibition of the CD24 immune checkpoint have been evaluated in the preclinical setting. In vivo studies are summarized in Table 3.

4.1.1. Monoclonal Antibodies

Monoclonal antibodies targeting CD24 have been used either with or without chemotherapy in various solid tumor models. ALB9 prevented lung metastases from CD24-overexpressing human urothelial cancer cells, with lung colonization restarting promptly after treatment discontinuation [34]. SWA11, which is another monoclonal antibody against CD24, reduced proliferation in human lung [21,105], ovarian [21,105], and pancreatic cancer cell lines [21] and impeded tumor growth in human colorectal cancer xenograft models [106]. Monotherapy with SWA11 has been shown to decrease tumor volume in several human xenograft models [21]. Moreover, pretreatment with SWA11 increased the antitumor efficacy of gemcitabine in vivo, particularly by promoting macrophage infiltration and disrupting angiogenesis [105]. SWA11 has been shown to increase the antitumor efficacy of multiple chemotherapy agents, including oxaliplatin, 5-fluorouracil, irinotecan, paclitaxel, and doxorubicin [106]. Dual CD24 inhibition with SWA11 and ML-5 suppressed the proliferation of CD24+ pancreatic cancer cell lines, with the antiproliferative effect correlating with CD24 expression levels [33]. Clone SN3 promoted phagocytosis in ovarian and breast cancer patient-derived CD24+ cell lines, and it increased survival in vivo through the macrophage-mediated inhibition of tumor growth [30].
The G7 monoclonal antibody designed against CD24 has demonstrated some antitumor activity as well [107,113]. Its combination with cetuximab exhibited enhanced antitumor efficacy, possibly through disruption of STAT3 signaling [107]. Concomitant manipulation of CD24 and CD47 has also been investigated as a potential treatment for glioblastoma in the preclinical setting [117]. The development of a bispecific antibody against the NK receptor ligand MICA and G7 has also shown promising preliminary results [108,118]. This approach employed the increased expression of CD24 in hepatocellular carcinoma tumor cells in order to recruit NK cells at the tumor site [108,118] and promote NK cell-mediated cytotoxicity, consequently showing substantial antitumor activity in vivo.
Recombinant antibodies targeting CD24 have also been tested. Single-chain variable fragments (scFvs), selected from a total RNA library from lymphocytes of breast cancer patients, showed high selectivity for CD24 and CD44 and produced a synergistic effect when administered in combination with epirubicin [109]. ScFvs have received FDA approval in malignancies, including blinatumomab for acute lymphoblastic leukemia [119], and represent an alternative method for targeting CD24.

4.1.2. Antibody–Drug Conjugates

Antibody–drug conjugates have also shown promising results in preclinical studies. As such, the conjugate of an anti-CD24 monoclonal antibody with deglycosylated ricin A-chain delayed tumor growth in a small cell lung cancer xenograft model [110]. A second antibody–deglycosylated ricin A-chain conjugate produced complete remissions that were durable and increased survival in a Burkitt’s lymphoma mouse model [111]. Anti-CD24 monoclonal antibodies have also been conjugated with Pseudomonas-derived exotoxin; this approach produced dose-dependent cytotoxicity in CD24-expressing colorectal cancer cells and inhibited tumor growth in xenograft models, with the results replicated in a second preclinical study [45,112].
A humanized murine anti-CD24 monoclonal antibody conjugated with monomethyl auristatin E (MMAE), a tubulin inhibitor, exhibited antitumor efficacy in mouse hepatocellular carcinoma models [113]. MMAE represents a validated conjugate candidate, that has demonstrated activity in hematologic malignancies and has gained regulatory approval by the FDA [120]. A conjugate bearing doxorubicin induced cell cycle arrest in CD24+ hepatocellular carcinoma cells and impeded tumor growth in mice [114]. Finally, an antibody–nitric oxide conjugate delayed hepatocellular carcinoma tumor growth in mice by nitrating the mitochondrial protein Cyt c and promoting apoptosis [115]. More importantly, the conjugated form exhibited superior antitumor activity as compared with the unconjugated anti-CD24 monoclonal antibody itself [115].

4.1.3. Chimeric Antigen Receptor (CAR) T Cell Therapy

Following the successful implementation of CAR T cell immunotherapy in hematologic malignancies [121], some preclinical studies have employed engineered immune cells to target CD24 in solid tumors. Anti-CD24 CAR T cell therapy was effective in reducing tumor growth and metastasis in human pancreatic adenocarcinoma xenografts in mice [116]. The treatment was effective even in CD24 subclone-bearing tumors [116], suggesting that targeting pancreatic cancer stem cells with the use of this approach could be a viable treatment strategy for the therapy of pancreatic cancer.
Beyond T cells, NK cells have also demonstrated cytotoxic activity against ovarian cancer cell lines and patient-derived ovarian cancer cells [122]. Another strategy was the use of dendritic cells loaded with antibody-coated cancer cells, which targets different surface antigens, including CD24, to cross-present tumor antigens to CD8+ T cells [123]. This approach promoted T cell-mediated cytotoxicity in melanoma and ovarian cancer cell lines.

4.2. Clinical Trials

To this day, two clinical trials evaluating CD24-inhibiting agents have been completed in patients with cancer. The first one was a single-arm phase 1/2 study that enrolled 58 patients with severe B cell lymphoproliferative disease after bone marrow or organ transplantation [124,125]. The patients received a combination of two monoclonal antibodies: ALB9 targeting CD24 and BL13 targeting CD21 [124,125]. Overall, the study treatment was well-tolerated, with the most common adverse events being grade ≥ 3 transient neutropenia (42%) and grade 2 fever (22%) during the first infusion [124,125]. Grade 3 sepsis, diarrhea, vomiting, and thrombocytopenia were each reported in one patient. Combination therapy showed substantial clinical activity, with complete remission achieved in 61% of the cases [125]. After a median follow-up of 61 months, the overall survival rate was 46% [125]. However, the study treatment showed limited activity in the central nervous system [124,125]. As a result, this strategy has not been explored any further, and current treatment options for B cell lymphoproliferative disease arising post transplantation include the reduction of immunosuppression, rituximab, chemotherapy, or their combination [126].
The second study was a single-arm, single-institution phase 1/2 study involving 36 patients with primary hepatocellular carcinoma that had been subjected to surgical resection [127]. Study participants received adjuvant therapy with autologous transfusions of dendritic cells and cytokine-induced T cells loaded with the CD24 peptide [127]. The treatment was safe, with the most common adverse event being transient fever (<grade 3) in 19% of the patients [127]. No grade 3 or higher adverse events were reported [127]. The 4-year overall survival rate was 47% and 53% in patients receiving study treatment two and four times, respectively [127].
Additional clinical trials evaluating agents that target the CD24 immune checkpoint in patients with melanoma or advanced solid tumors have been registered (NCT04552704, NCT04060407). Τhese trials used a recombinant fusion protein, CD24Fc, which activates the CD24/Siglec-10 pathway [128], in combination with immunotherapy; their aim was to evaluate whether combination therapy would reduce the incidence and/or severity of immune-related adverse events. One of these trials was terminated early (NCT04552704), while the other was withdrawn before recruitment started (NCT04060407). Clinical trials of CD24-targeting agents in malignancies are summarized in Table 4.

5. Conclusions

CD24 represents a promising target for cancer immunotherapy. The overexpression of CD24 has been documented in several tumor types and the activation of the CD24/Siglec-10 axis has been shown to promote tumor immune evasion through the suppression of the cytotoxic T cell function and macrophage-mediated phagocytosis. Preclinical efforts to inhibit CD24 signaling have employed monoclonal antibodies, antibody–drug conjugates, and CAR T cell therapy. Although clinical evidence regarding the efficacy of CD24 blockade is currently limited, the compelling preclinical data in various tumor types—including but not limited to those with dismal prognosis and limited efficacy of PD-1/PD-L1 axis inhibition such as in pancreatic and ovarian cancer—as well as the pressing clinical need for novel treatment strategies might provide enough justification for the accelerated clinical testing of CD24 axis inhibitors. A potential caveat to that would be the lack of established biomarkers for the prediction of response to treatment with anti-CD24 antibodies. There is currently no standardized method for determining CD24 positivity, with some studies using flow cytometry and others employing immunohistochemical expression, with substantial heterogeneity. Finally, more preclinical data are required to delineate a potential role for a concomitant CD24 and PD-1/PD-L1 axis blockade.

Author Contributions

Conceptualization: I.A.V.; data curation: E.P. and N.K.S.; writing—original draft: E.P. and I.A.V.; writing—review and editing: E.P., N.K.S., A.C., E.K. and I.A.V. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Esfahani, K.; Roudaia, L.; Buhlaiga, N.; Del Rincon, S.V.; Papneja, N.; Miller, W.H. A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future. Curr. Oncol. 2020, 27, 87–97. [Google Scholar] [CrossRef] [PubMed]
  2. Mellman, I.; Coukos, G.; Dranoff, G. Cancer immunotherapy comes of age. Nature 2011, 480, 480–489. [Google Scholar] [CrossRef] [PubMed]
  3. Qin, S.; Xu, L.; Yi, M.; Yu, S.; Wu, K.; Luo, S. Novel immune checkpoint targets: Moving beyond PD-1 and CTLA-4. Mol. Cancer 2019, 18, 155. [Google Scholar] [CrossRef]
  4. Altevogt, P.; Sammar, M.; Hüser, L.; Kristiansen, G. Novel insights into the function of CD24: A driving force in cancer. Int. J. Cancer 2021, 148, 546–559. [Google Scholar] [CrossRef] [PubMed]
  5. Fang, X.; Zheng, P.; Tang, J.; Liu, Y. CD24: From A to Z. Cell. Mol. Immunol. 2010, 7, 100–103. [Google Scholar] [CrossRef] [Green Version]
  6. Liu, Y.; Jones, B.; Aruffo, A.; Sullivan, K.M.; Linsley, P.S.; Janeway, C.A. Heat-stable antigen is a costimulatory molecule for CD4 T cell growth. J. Exp. Med. 1992, 175, 437–445. [Google Scholar] [CrossRef] [Green Version]
  7. Suzuki, T.; Kiyokawa, N.; Taguchi, T.; Sekino, T.; Katagiri, Y.U.; Fujimoto, J. CD24 Induces Apoptosis in Human B Cells Via the Glycolipid-Enriched Membrane Domains/Rafts-Mediated Signaling System. J. Immunol. 2001, 166, 5567–5577. [Google Scholar] [CrossRef] [Green Version]
  8. Chappel, M.S.; Hough, M.R.; Mittel, A.; Takei, F.; Kay, R.; Humphries, R.K. Cross-linking the murine heat-stable antigen induces apoptosis in B cell precursors and suppresses the anti-CD40-induced proliferation of mature resting B lymphocytes. J. Exp. Med. 1996, 184, 1639–1649. [Google Scholar] [CrossRef] [PubMed]
  9. Wu, H.; Su, Z.; Barnie, P.A. The role of B regulatory (B10) cells in inflammatory disorders and their potential as therapeutic targets. Int. Immunopharmacol. 2020, 78, 106111. [Google Scholar] [CrossRef]
  10. Shi, Y.; Zhu, J.; Liu, J.-Q.; Talebian, F.; Li, M.; Bai, X.-F. CD24 is expressed on FoxP3+ regulatory T cells and regulates their function. Am. J. Transl. Res. 2022, 14, 2291–2300. [Google Scholar]
  11. Kim, T.S.; Gorski, S.A.; Hahn, S.; Murphy, K.M.; Braciale, T.J. Distinct Dendritic Cell Subsets Dictate the Fate Decision between Effector and Memory CD8+ T Cell Differentiation by a CD24-Dependent Mechanism. Immunity 2014, 40, 400–413. [Google Scholar] [CrossRef] [Green Version]
  12. Li, O.; Chang, X.; Zhang, H.; Kocak, E.; Ding, C.; Zheng, P.; Liu, Y. Massive and destructive T cell response to homeostatic cue in CD24-deficient lymphopenic hosts. J. Exp. Med. 2006, 203, 1713–1720. [Google Scholar] [CrossRef] [PubMed]
  13. Kristiansen, G.; Sammar, M.; Altevogt, P. Tumour Biological Aspects of CD24, A Mucin-Like Adhesion Molecule. J. Mol. Histol. 2004, 35, 255–262. [Google Scholar] [CrossRef] [PubMed]
  14. Aigner, S.; Ruppert, M.; Hubbe, M.; Sammar, M.; Sthoeger, Z.; Butcher, E.C.; Vestweber, D.; Altevogt, P.; Kaufmann, S.H.E. Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. Int. Immunol. 1995, 7, 1557–1565. [Google Scholar] [CrossRef] [PubMed]
  15. Runz, S.; Mierke, C.T.; Joumaa, S.; Behrens, J.; Fabry, B.; Altevogt, P. CD24 induces localization of β1 integrin to lipid raft domains. Biochem. Biophys. Res. Commun. 2008, 365, 35–41. [Google Scholar] [CrossRef]
  16. Sammar, M.; Gulbins, E.; Hilbert, K.; Lang, F.; Altevogt, P. Mouse CD24 as a Signaling Molecule for Integrin-Mediated Cell Binding: Functional and Physical Association with src-Kinases. Biochem. Biophys. Res. Commun. 1997, 234, 330–334. [Google Scholar] [CrossRef] [PubMed]
  17. Pruszak, J.; Ludwig, W.; Blak, A.; Alavian, K.; Isacson, O. CD15, CD24, and CD29 Define a Surface Biomarker Code for Neural Lineage Differentiation of Stem Cells. Stem Cells 2009, 27, 2928–2940. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. Gilliam, D.T.; Menon, V.; Bretz, N.P.; Pruszak, J. The CD24 surface antigen in neural development and disease. Neurobiol. Dis. 2017, 99, 133–144. [Google Scholar] [CrossRef] [PubMed]
  19. Poncet, C.; Frances, V.; Gristina, R.; Scheiner, C.; Pellissier, J.-F.; Figarella-Branger, D. CD24, a glycosylphosphatidylinositol-anchored molecule, is transiently expressed during the development of human central nervous system and is a marker of human neural cell lineage tumors. Acta Neuropathol. 1996, 91, 400–408. [Google Scholar] [CrossRef]
  20. Kleene, R.; Yang, H.; Kutsche, M.; Schachner, M. The Neural Recognition Molecule L1 Is a Sialic Acid-binding Lectin for CD24, Which Induces Promotion and Inhibition of Neurite Outgrowth*. J. Biol. Chem. 2001, 276, 21656–21663. [Google Scholar] [CrossRef] [Green Version]
  21. Bretz, N.P.; Salnikov, A.V.; Perne, C.; Keller, S.; Wang, X.; Mierke, C.T.; Fogel, M.; Erbe-Hofmann, N.; Schlange, T.; Moldenhauer, G.; et al. CD24 controls Src/STAT3 activity in human tumors. Cell. Mol. Life Sci. CMLS 2012, 69, 3863–3879. [Google Scholar] [CrossRef] [PubMed]
  22. Deng, W.; Gu, L.; Li, X.; Zheng, J.; Zhang, Y.; Duan, B.; Cui, J.; Dong, J.; Du, J. CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells. J. Transl. Med. 2016, 14, 32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Hosonaga, M.; Arima, Y.; Sugihara, E.; Kohno, N.; Saya, H. Expression of CD24 is associated with HER2 expression and supports HER2-Akt signaling in HER2-positive breast cancer cells. Cancer Sci. 2014, 105, 779–787. [Google Scholar] [CrossRef]
  24. Smith, S.C.; Oxford, G.; Wu, Z.; Nitz, M.D.; Conaway, M.; Frierson, H.F.; Hampton, G.; Theodorescu, D. The metastasis-associated gene CD24 is regulated by Ral GTPase and is a mediator of cell proliferation and survival in human cancer. Cancer Res. 2006, 66, 1917–1922. [Google Scholar] [CrossRef] [Green Version]
  25. Eyvazi, S.; Kazemi, B.; Dastmalchi, S.; Bandehpour, M. Involvement of CD24 in Multiple Cancer Related Pathways Makes It an Interesting New Target for Cancer Therapy. Curr. Cancer Drug Targets 2018, 18, 328–336. [Google Scholar] [CrossRef]
  26. Wang, W.; Wang, X.; Peng, L.; Deng, Q.; Liang, Y.; Qing, H.; Jiang, B. CD24-dependent MAPK pathway activation is required for colorectal cancer cell proliferation. Cancer Sci. 2010, 101, 112–119. [Google Scholar] [CrossRef] [PubMed]
  27. Lu, S.; Yao, Y.; Xu, G.; Zhou, C.; Zhang, Y.; Sun, J.; Jiang, R.; Shao, Q.; Chen, Y. CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma. Cell Death Dis. 2018, 9, 646. [Google Scholar] [CrossRef] [PubMed]
  28. Yin, S.-S.; Gao, F.-H. Molecular Mechanism of Tumor Cell Immune Escape Mediated by CD24/Siglec-10. Front. Immunol. 2020, 11, 1324. [Google Scholar] [CrossRef]
  29. Song, Y.; Lu, M.; Feng, L.; Chen, Q.; Huang, H.; Lin, Q. Identification of potential immunotherapy biomarkers for breast cancer by bioinformatics analysis. Biosci. Rep. 2022, 42, BSR20212035. [Google Scholar] [CrossRef]
  30. Barkal, A.A.; Brewer, R.E.; Markovic, M.; Kowarsky, M.; Barkal, S.A.; Zaro, B.W.; Krishnan, V.; Hatakeyama, J.; Dorigo, O.; Barkal, L.J.; et al. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature 2019, 572, 392–396. [Google Scholar] [CrossRef] [PubMed]
  31. Jackson, D.; Waibel, R.; Weber, E.; Bell, J.; Stahel, R.A. CD24, a signal-transducing molecule expressed on human B cells, is a major surface antigen on small cell lung carcinomas. Cancer Res. 1992, 52, 5264–5270. [Google Scholar] [PubMed]
  32. Sagiv, E.; Memeo, L.; Karin, A.; Kazanov, D.; Jacob–Hirsch, J.; Mansukhani, M.; Rechavi, G.; Hibshoosh, H.; Arber, N. CD24 Is a New Oncogene, Early at the Multistep Process of Colorectal Cancer Carcinogenesis. Gastroenterology 2006, 131, 630–639. [Google Scholar] [CrossRef] [PubMed]
  33. Sagiv, E.; Kazanov, D.; Arber, N. CD24 plays an important role in the carcinogenesis process of the pancreas. Biomed. Pharmacother. 2006, 60, 280–284. [Google Scholar] [CrossRef]
  34. Overdevest, J.B.; Thomas, S.; Kristiansen, G.; Hansel, D.E.; Smith, S.C.; Theodorescu, D. CD24 offers a therapeutic target for control of bladder cancer metastasis based on a requirement for lung colonization. Cancer Res. 2011, 71, 3802–3811. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. Kristiansen, G.; Pilarsky, C.; Pervan, J.; Stürzebecher, B.; Stephan, C.; Jung, K.; Loening, S.; Rosenthal, A.; Dietel, M. CD24 expression is a significant predictor of PSA relapse and poor prognosis in low grade or organ confined prostate cancer. Prostate 2004, 58, 183–192. [Google Scholar] [CrossRef]
  36. Mishra, S.; Tiwari, V.; Arora, A.; Gupta, S.; Anand, N.; Husain, N. Increased Expression of Oct4, Nanog and CD24 Predicts Poor Response to Chemo-Radiotherapy and Unfavourable Prognosis in Locally Advanced Oral Squamous Cell Carcinoma. Asian Pac. J. Cancer Prev. APJCP 2020, 21, 2539–2547. [Google Scholar] [CrossRef] [PubMed]
  37. Sandén, E.; Dyberg, C.; Krona, C.; Visse, E.; Carén, H.; Northcott, P.A.; Kool, M.; Ståhl, N.; Persson, A.; Englund, E.; et al. Aberrant immunostaining pattern of the CD24 glycoprotein in clinical samples and experimental models of pediatric medulloblastomas. J. Neurooncol. 2015, 123, 1–13. [Google Scholar] [CrossRef] [PubMed]
  38. Boon, K.; Edwards, J.B.; Siu, I.-M.; Olschner, D.; Eberhart, C.G.; Marra, M.A.; Strausberg, R.L.; Riggins, G.J. Comparison of medulloblastoma and normal neural transcriptomes identifies a restricted set of activated genes. Oncogene 2003, 22, 7687–7694. [Google Scholar] [CrossRef] [Green Version]
  39. Uckun, F.M.; Song, C.W. Lack of CD24 antigen expression in B-lineage acute lymphoblastic leukemia is associated with intrinsic radiation resistance of primary clonogenic blasts. Blood 1993, 81, 1323–1332. [Google Scholar] [CrossRef] [Green Version]
  40. Raife, T.J.; Lager, D.J.; Kemp, J.D.; Dick, F.R. Expression of CD24 (BA-1) Predicts Monocytic Lineage in Acute Myeloid Leukemia. Am. J. Clin. Pathol. 1994, 101, 296–299. [Google Scholar] [CrossRef]
  41. Gross Even-Zohar, N.; Pick, M.; Hofstetter, L.; Shaulov, A.; Nachmias, B.; Lebel, E.; Gatt, M.E. CD24 Is a Prognostic Marker for Multiple Myeloma Progression and Survival. J. Clin. Med. 2022, 11, 2913. [Google Scholar] [CrossRef] [PubMed]
  42. Nersisyan, S.; Ahlers, A.-K.; Lange, T.; Wicklein, D.; Galatenko, A.; Bohnenberger, H.; Elakad, O.; Conradi, L.-C.; Genduso, S.; Maar, H.; et al. Low expression of CD24 is associated with poor survival in colorectal cancer. Biochimie 2022, 192, 91–101. [Google Scholar] [CrossRef]
  43. Choi, Y.-L.; Lee, S.-H.; Kwon, G.-Y.; Park, C.-K.; Han, J.-J.; Choi, J.S.; Choi, H.Y.; Kim, S.-H.; Shin, Y.K. Overexpression of CD24: Association with invasiveness in urothelial carcinoma of the bladder. Arch. Pathol. Lab. Med. 2007, 131, 275–281. [Google Scholar] [CrossRef] [PubMed]
  44. Baumann, P.; Cremers, N.; Kroese, F.; Orend, G.; Chiquet-Ehrismann, R.; Uede, T.; Yagita, H.; Sleeman, J.P. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res. 2005, 65, 10783–10793. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Shapira, S.; Kazanov, D.; Weisblatt, S.; Starr, A.; Arber, N.; Kraus, S. The CD24 protein inducible expression system is an ideal tool to explore the potential of CD24 as an oncogene and a target for immunotherapy in vitro and in vivo. J. Biol. Chem. 2011, 286, 40548–40555. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Aigner, S.; Sthoeger, Z.M.; Fogel, M.; Weber, E.; Zarn, J.; Ruppert, M.; Zeller, Y.; Vestweber, D.; Stahel, R.; Sammar, M.; et al. CD24, a Mucin-Type Glycoprotein, Is a Ligand for P-Selectin on Human Tumor Cells. Blood 1997, 89, 3385–3395. [Google Scholar] [CrossRef]
  47. Myung, J.H.; Gajjar, K.A.; Pearson, R.M.; Launiere, C.A.; Eddington, D.T.; Hong, S. Direct Measurements on CD24-Mediated Rolling of Human Breast Cancer MCF-7 Cells on E-selectin. Anal. Chem. 2011, 83, 1078–1083. [Google Scholar] [CrossRef] [Green Version]
  48. Thomas, S.; Harding, M.A.; Smith, S.C.; Overdevest, J.B.; Nitz, M.D.; Frierson, H.F.; Tomlins, S.A.; Kristiansen, G.; Theodorescu, D. CD24 Is an Effector of HIF-1–Driven Primary Tumor Growth and Metastasis. Cancer Res. 2012, 72, 5600–5612. [Google Scholar] [CrossRef] [Green Version]
  49. Kraus, S.; Shapira, S.; Kazanov, D.; Naumov, I.; Moshkowitz, M.; Santo, E.; Galazan, L.; Geva, R.; Shmueli, E.; Hallack, A.; et al. Predictive Levels of CD24 in Peripheral Blood Leukocytes for the Early Detection of Colorectal Adenomas and Adenocarcinomas. Dis. Markers 2015, 2015, e916098. [Google Scholar] [CrossRef] [Green Version]
  50. Shapira, S.; Kazanov, D.; Mdah, F.; Yaakobi, H.; Herishanu, Y.; Perry, C.; Avivi, I.; Itchaki, G.; Shacham-Abulafia, A.; Raanani, P.; et al. Feasibly of CD24/CD11b as a Screening Test for Hematological Malignancies. J. Pers. Med. 2021, 11, 724. [Google Scholar] [CrossRef]
  51. Perry, J.M.; Tao, F.; Roy, A.; Lin, T.; He, X.C.; Chen, S.; Lu, X.; Nemechek, J.; Ruan, L.; Yu, X.; et al. Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells. Nat. Cell Biol. 2020, 22, 689–700. [Google Scholar] [CrossRef]
  52. Sun, J.; Feng, D.; Xi, H.; Luo, J.; Zhou, Z.; Liu, Q.; Chen, Y.; Shao, Q. CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy. Mol. Oncol. 2020, 14, 1740–1759. [Google Scholar] [CrossRef]
  53. Sui, X.; Chen, R.; Wang, Z.; Huang, Z.; Kong, N.; Zhang, M.; Han, W.; Lou, F.; Yang, J.; Zhang, Q.; et al. Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis. 2013, 4, e838. [Google Scholar] [CrossRef] [PubMed]
  54. Huth, H.W.; Castro-Gomes, T.; de Goes, A.M.; Ropert, C. Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer. Sci. Rep. 2021, 11, 17077. [Google Scholar] [CrossRef] [PubMed]
  55. Ju, J.; Jang, K.; Lee, K.; Kim, M.; Kim, J.; Yi, J.Y.; Noh, D.-Y.; Shin, I. CD24 enhances DNA damage-induced apoptosis by modulating NF-κB signaling in CD44-expressing breast cancer cells. Carcinogenesis 2011, 32, 1474–1483. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Modur, V.; Joshi, P.; Nie, D.; Robbins, K.T.; Khan, A.U.; Rao, K. CD24 Expression May Play a Role as a Predictive Indicator and a Modulator of Cisplatin Treatment Response in Head and Neck Squamous Cellular Carcinoma. PLoS ONE 2016, 11, e0156651. [Google Scholar] [CrossRef] [Green Version]
  57. Koh, J.; Lee, S.; Park, H.; Lee, H.J.; Cho, N.H.; Kim, J. Susceptibility of CD24(+) ovarian cancer cells to anti-cancer drugs and natural killer cells. Biochem. Biophys. Res. Commun. 2012, 427, 373–378. [Google Scholar] [CrossRef] [PubMed]
  58. Jia, Y.; Gu, D.; Wan, J.; Yu, B.; Zhang, X.; Chiorean, E.G.; Wang, Y.; Xie, J. The role of GLI-SOX2 signaling axis for gemcitabine resistance in pancreatic cancer. Oncogene 2019, 38, 1764–1777. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  59. Soni, P.; Qayoom, S.; Husain, N.; Kumar, P.; Chandra, A.; Ojha, B.K.; Gupta, R.K. CD24 and Nanog expression in Stem Cells in Glioblastoma: Correlation with Response to Chemoradiation and Overall Survival. Asian Pac. J. Cancer Prev. APJCP 2017, 18, 2215–2219. [Google Scholar] [CrossRef]
  60. Pandey, V.; Jung, Y.; Kang, J.; Steiner, M.; Qian, P.-X.; Banerjee, A.; Mitchell, M.D.; Wu, Z.-S.; Zhu, T.; Liu, D.-X.; et al. Artemin Reduces Sensitivity to Doxorubicin and Paclitaxel in Endometrial Carcinoma Cells through Specific Regulation of CD24. Transl. Oncol. 2010, 3, 218–229, IN1–IN5. [Google Scholar] [CrossRef] [Green Version]
  61. Chen, Y.; Song, J.; Jiang, Y.; Yu, C.; Ma, Z. Predictive value of CD44 and CD24 for prognosis and chemotherapy response in invasive breast ductal carcinoma. Int. J. Clin. Exp. Pathol. 2015, 8, 11287–11295. [Google Scholar] [PubMed]
  62. Horiguchi, K.; Toi, M.; Horiguchi, S.-I.; Sugimoto, M.; Naito, Y.; Hayashi, Y.; Ueno, T.; Ohno, S.; Funata, N.; Kuroi, K.; et al. Predictive value of CD24 and CD44 for neoadjuvant chemotherapy response and prognosis in primary breast cancer patients. J. Med. Dent. Sci. 2010, 57, 165–175. [Google Scholar] [CrossRef] [Green Version]
  63. Marmé, F.; Werft, W.; Walter, A.; Keller, S.; Wang, X.; Benner, A.; Burwinkel, B.; Sinn, P.; Hug, S.; Sohn, C.; et al. CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer. Breast Cancer Res. Treat. 2012, 132, 819–831. [Google Scholar] [CrossRef] [PubMed]
  64. Hüser, L.; Sachindra, S.; Granados, K.; Federico, A.; Larribère, L.; Novak, D.; Umansky, V.; Altevogt, P.; Utikal, J. SOX2-mediated upregulation of CD24 promotes adaptive resistance toward targeted therapy in melanoma. Int. J. Cancer 2018, 143, 3131–3142. [Google Scholar] [CrossRef] [Green Version]
  65. Kitazono, S.; Takiguchi, Y.; Ashinuma, H.; Saito-Kitazono, M.; Kitamura, A.; Chiba, T.; Sakaida, E.; Sekine, I.; Tada, Y.; Kurosu, K.; et al. Effect of metformin on residual cells after chemotherapy in a human lung adenocarcinoma cell line. Int. J. Oncol. 2013, 43, 1846–1854. [Google Scholar] [CrossRef] [Green Version]
  66. Liu, Z.; Gao, W. Overcoming acquired resistance of gefitinib in lung cancer cells without T790M by AZD9291 or Twist1 knockdown in vitro and in vivo. Arch. Toxicol. 2019, 93, 1555–1571. [Google Scholar] [CrossRef]
  67. Stremitzer, S.; Sunakawa, Y.; Zhang, W.; Yang, D.; Ning, Y.; Stintzing, S.; Sebio, A.; Yamauchi, S.; Matsusaka, S.; El-Khoueiry, R.; et al. Variations in genes involved in immune response checkpoints and association with outcomes in patients with resected colorectal liver metastases. Pharm. J. 2015, 15, 521–529. [Google Scholar] [CrossRef] [PubMed]
  68. van Houtum, E.J.H.; Büll, C.; Cornelissen, L.A.M.; Adema, G.J. Siglec Signaling in the Tumor Microenvironment. Front. Immunol. 2021, 12, 790317. [Google Scholar] [CrossRef]
  69. Crocker, P.R.; Paulson, J.C.; Varki, A. Siglecs and their roles in the immune system. Nat. Rev. Immunol. 2007, 7, 255–266. [Google Scholar] [CrossRef] [PubMed]
  70. Chen, G.-Y.; Tang, J.; Zheng, P.; Liu, Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 2009, 323, 1722–1725. [Google Scholar] [CrossRef] [Green Version]
  71. Tang, D.; Kang, R.; Coyne, C.B.; Zeh, H.J.; Lotze, M.T. PAMPs and DAMPs: Signal 0s that spur autophagy and immunity. Immunol. Rev. 2012, 249, 158–175. [Google Scholar] [CrossRef] [PubMed]
  72. Liu, Y.; Chen, G.-Y.; Zheng, P. CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns. Trends Immunol. 2009, 30, 557–561. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Wang, L.; Lin, S.; Rammohan, K.W.; Liu, Z.; Liu, J.; Liu, R.; Guinther, N.; Lima, J.; Zhou, Q.; Wang, T.; et al. A Dinucleotide Deletion in CD24 Confers Protection against Autoimmune Diseases. PLoS Genet. 2007, 3, e49. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Zheng, P.; Liu, Y.; Chen, H.; Devenport, M.; Reddy, P.; Farag, S.S.; Devine, S.M.; Jaglowski, S.; Uberti, J.; Braun, T.; et al. Targeting Danger Associated Molecular Pattern (DAMP) with CD24Fc to Reduce Acute Gvhd: Study Design on a Randomized Double Blind Placebo Controlled Phase III Clinical Trial (CATHY Study). Biol. Blood Marrow Transplant. 2020, 26, S180–S181. [Google Scholar] [CrossRef]
  75. Eckhardt, C.M.; O’Donnell, M.R. CD24Fc: An emerging COVID-19 therapy. Lancet Infect. Dis. 2022, 22, 565–567. [Google Scholar] [CrossRef]
  76. Liu, Y.; Chen, G.-Y.; Zheng, P. Sialoside-based pattern recognitions discriminating infections from tissue injuries. Curr. Opin. Immunol. 2011, 23, 41–45. [Google Scholar] [CrossRef] [Green Version]
  77. Munkley, J.; Scott, E. Targeting Aberrant Sialylation to Treat Cancer. Medicines 2019, 6, 102. [Google Scholar] [CrossRef] [Green Version]
  78. Chen, G.-Y.; Chen, X.; King, S.; Cavassani, K.A.; Cheng, J.; Zheng, X.; Cao, H.; Yu, H.; Qu, J.; Fang, D.; et al. Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nat. Biotechnol. 2011, 29, 428–435. [Google Scholar] [CrossRef]
  79. Zhang, C.; Zhang, J.; Liang, F.; Guo, H.; Gao, S.; Yang, F.; Guo, H.; Wang, G.; Wang, W.; Zhou, G. Innate immune checkpoint Siglec10 in cancers: Mining of comprehensive omics data and validation in patient samples. Front. Med. 2022, 1–14. [Google Scholar] [CrossRef]
  80. Meesmann, H.M.; Fehr, E.-M.; Kierschke, S.; Herrmann, M.; Bilyy, R.; Heyder, P.; Blank, N.; Krienke, S.; Lorenz, H.-M.; Schiller, M. Decrease of sialic acid residues as an eat-me signal on the surface of apoptotic lymphocytes. J. Cell Sci. 2010, 123, 3347–3356. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  81. Lin, C.-Y.; Tsai, C.-L.; Chao, A.; Lee, L.-Y.; Chen, W.-C.; Tang, Y.-H.; Chao, A.-S.; Lai, C.-H. Nucleophosmin/B23 promotes endometrial cancer cell escape from macrophage phagocytosis by increasing CD24 expression. J. Mol. Med. Berl. Ger. 2021, 99, 1125–1137. [Google Scholar] [CrossRef] [PubMed]
  82. Ames, E.; Canter, R.J.; Grossenbacher, S.K.; Mac, S.; Chen, M.; Smith, R.C.; Hagino, T.; Perez-Cunningham, J.; Sckisel, G.D.; Urayama, S.; et al. NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype. J. Immunol. 2015, 195, 4010–4019. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  83. Yin, T.; Wang, G.; He, S.; Liu, Q.; Sun, J.; Wang, Y. Human cancer cells with stem cell-like phenotype exhibit enhanced sensitivity to the cytotoxicity of IL-2 and IL-15 activated natural killer cells. Cell. Immunol. 2016, 300, 41–45. [Google Scholar] [CrossRef] [PubMed]
  84. Zhang, P.; Lu, X.; Tao, K.; Shi, L.; Li, W.; Wang, G.; Wu, K. Siglec-10 is associated with survival and natural killer cell dysfunction in hepatocellular carcinoma. J. Surg. Res. 2015, 194, 107–113. [Google Scholar] [CrossRef] [PubMed]
  85. Alsuliman, A.; Colak, D.; Al-Harazi, O.; Fitwi, H.; Tulbah, A.; Al-Tweigeri, T.; Al-Alwan, M.; Ghebeh, H. Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: Significance in claudin-low breast cancer cells. Mol. Cancer 2015, 14, 149. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  86. Xiao, X.; Lao, X.-M.; Chen, M.-M.; Liu, R.-X.; Wei, Y.; Ouyang, F.-Z.; Chen, D.-P.; Zhao, X.-Y.; Zhao, Q.; Li, X.-F.; et al. PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression. Cancer Discov. 2016, 6, 546–559. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  87. Liu, M.; Wang, X.; Zhang, P.; Su, J.; Du, X.; Zhang, Y.; Liu, Y.; Zheng, P. 813 CD24Fc ameliorates immune-related adverse events while preserving anti-tumor therapeutic effect. J. Immunother. Cancer 2021, 9, A1054. [Google Scholar] [CrossRef]
  88. Kong, T.; Ahn, R.; Yang, K.; Zhu, X.; Fu, Z.; Morin, G.; Bramley, R.; Cliffe, N.C.; Xue, Y.; Kuasne, H.; et al. CD44 Promotes PD-L1 Expression and Its Tumor-Intrinsic Function in Breast and Lung Cancers. Cancer Res. 2020, 80, 444–457. [Google Scholar] [CrossRef]
  89. Naor, D.; Wallach-Dayan, S.B.; Zahalka, M.A.; Sionov, R.V. CHAPTER 8-Involvement of CD44, a Molecule with a Thousand Faces, in Cancer Dissemination. In Hyaluronan in Cancer Biology; Stern, R., Ed.; Academic Press: San Diego, CA, USA, 2009; pp. 127–146. ISBN 978-0-12-374178-3. [Google Scholar]
  90. Naor, D.; Sionov, R.V.; Ish-Shalom, D. CD44: Structure, Function and Association with the Malignant Process. Adv. Cancer Res. 1997, 71, 241–319. [Google Scholar] [CrossRef] [PubMed]
  91. Jaggupilli, A.; Elkord, E. Significance of CD44 and CD24 as Cancer Stem Cell Markers: An Enduring Ambiguity. Clin. Dev. Immunol. 2012, 2012, e708036. [Google Scholar] [CrossRef] [Green Version]
  92. Napier, S.L.; Healy, Z.R.; Schnaar, R.L.; Konstantopoulos, K. Selectin Ligand Expression Regulates the Initial Vascular Interactions of Colon Carcinoma Cells: THE ROLES OF CD44V AND ALTERNATIVE SIALOFUCOSYLATED SELECTIN LIGANDS*. J. Biol. Chem. 2007, 282, 3433–3441. [Google Scholar] [CrossRef] [Green Version]
  93. Mrass, P.; Kinjyo, I.; Ng, L.G.; Reiner, S.L.; Puré, E.; Weninger, W. CD44 Mediates Successful Interstitial Navigation by Killer T Cells and Enables Efficient Antitumor Immunity. Immunity 2008, 29, 971–985. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  94. Klement, J.D.; Paschall, A.V.; Redd, P.S.; Ibrahim, M.L.; Lu, C.; Yang, D.; Celis, E.; Abrams, S.I.; Ozato, K.; Liu, K. An osteopontin/CD44 immune checkpoint controls CD8+ T cell activation and tumor immune evasion. J. Clin. Investig. 2018, 128, 5549–5560. [Google Scholar] [CrossRef]
  95. Shurin, M.R. Osteopontin controls immunosuppression in the tumor microenvironment. J. Clin. Investig. 2018, 128, 5209–5212. [Google Scholar] [CrossRef] [PubMed]
  96. Velasco-Velázquez, M.A.; Homsi, N.; De La Fuente, M.; Pestell, R.G. Breast cancer stem cells. Int. J. Biochem. Cell Biol. 2012, 44, 573–577. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  97. Hurt, E.M.; Kawasaki, B.T.; Klarmann, G.J.; Thomas, S.B.; Farrar, W.L. CD44+CD24− prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br. J. Cancer 2008, 98, 756–765. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  98. Sun, H.; Jia, J.; Wang, X.; Ma, B.; Di, L.; Song, G.; Ren, J. CD44+/CD24− breast cancer cells isolated from MCF-7 cultures exhibit enhanced angiogenic properties. Clin. Transl. Oncol. 2013, 15, 46–54. [Google Scholar] [CrossRef] [PubMed]
  99. El-Ashmawy, N.E.; Salem, M.L.; Khedr, E.G.; El-Zamarany, E.A.; Ibrahim, A.O. Dual-targeted therapeutic strategy combining CSC-DC-based vaccine and cisplatin overcomes chemo-resistance in experimental mice model. Clin. Transl. Oncol. Off. Publ. Fed. Span. Oncol. Soc. Natl. Cancer Inst. Mex. 2020, 22, 1155–1165. [Google Scholar] [CrossRef]
  100. Mirza, S.; Jain, N.; Rawal, R. Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy. Tumor Biol. 2017, 39, 1010428317695915. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  101. Meng, E.; Long, B.; Sullivan, P.; McClellan, S.; Finan, M.A.; Reed, E.; Shevde, L.; Rocconi, R.P. CD44+/CD24− ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival. Clin. Exp. Metastasis 2012, 29, 939–948. [Google Scholar] [CrossRef]
  102. Li, C.; Heidt, D.G.; Dalerba, P.; Burant, C.F.; Zhang, L.; Adsay, V.; Wicha, M.; Clarke, M.F.; Simeone, D.M. Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67, 1030–1037. [Google Scholar] [CrossRef] [Green Version]
  103. Tanida, T.; Tanemura, M.; Miyoshi, E.; Nagano, H.; Furukawa, K.; Nonaka, Y.; Akita, H.; Hama, N.; Wada, H.; Kawamoto, K.; et al. Pancreatic cancer immunotherapy using a tumor lysate vaccine, engineered to express α-gal epitopes, targets pancreatic cancer stem cells. Int. J. Oncol. 2015, 46, 78–90. [Google Scholar] [CrossRef]
  104. Dashti, A.; Ebrahimi, M.; Hadjati, J.; Memarnejadian, A.; Moazzeni, S.M. Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses. Cancer Lett. 2016, 374, 175–185. [Google Scholar] [CrossRef]
  105. Salnikov, A.V.; Bretz, N.P.; Perne, C.; Hazin, J.; Keller, S.; Fogel, M.; Herr, I.; Schlange, T.; Moldenhauer, G.; Altevogt, P. Antibody targeting of CD24 efficiently retards growth and influences cytokine milieu in experimental carcinomas. Br. J. Cancer 2013, 108, 1449–1459. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  106. Sagiv, E.; Starr, A.; Rozovski, U.; Khosravi, R.; Altevogt, P.; Wang, T.; Arber, N. Targeting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or small interfering RNA. Cancer Res. 2008, 68, 2803–2812. [Google Scholar] [CrossRef] [Green Version]
  107. Chen, Z.; Wang, T.; Tu, X.; Xie, W.; He, H.; Wang, M.; Zhang, J. Antibody-based targeting of CD24 enhances antitumor effect of cetuximab via attenuating phosphorylation of Src/STAT3. Biomed. Pharmacother. 2017, 90, 427–436. [Google Scholar] [CrossRef]
  108. Wang, T.; Sun, F.; Xie, W.; Tang, M.; He, H.; Jia, X.; Tian, X.; Wang, M.; Zhang, J. A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma. Cancer Lett. 2016, 372, 166–178. [Google Scholar] [CrossRef] [PubMed]
  109. Huang, S.; Feng, L.; An, G.; Zhang, X.; Zhao, Z.; Han, R.; Lei, F.; Zhang, Y.; Luo, A.; Jing, X.; et al. Ribosome display and selection of single-chain variable fragments effectively inhibit growth and progression of microspheres in vitro and in vivo. Cancer Sci. 2018, 109, 1503–1512. [Google Scholar] [CrossRef]
  110. Zangemeister-Wittke, U.; Lehmann, H.P.; Waibel, R.; Wawrzynczak, E.J.; Stahel, R.A. Action of a CD24-specific deglycosylated ricin-A-chain immunotoxin in conventional and novel models of small-cell-lung-cancer xenograft. Int. J. Cancer 1993, 53, 521–528. [Google Scholar] [CrossRef] [PubMed]
  111. Schnell, R.; Katouzi, A.A.; Linnartz, C.; Schoen, G.; Drillich, S.; Hansmann, M.-L.; Schiefer, D.; Barth, S.; Zangemeister-Wittke, U.; Stahel, R.A.; et al. Potent anti-tumor effects of an anti-CD24 ricin A-chain immunotoxin in vitro and in a disseminated human Burkitt’s lymphoma model in SCID mice. Int. J. Cancer 1996, 66, 526–531. [Google Scholar] [CrossRef]
  112. Shapira, S.; Shapira, A.; Starr, A.; Kazanov, D.; Kraus, S.; Benhar, I.; Arber, N. An immunoconjugate of anti-CD24 and Pseudomonas exotoxin selectively kills human colorectal tumors in mice. Gastroenterology 2011, 140, 935–946. [Google Scholar] [CrossRef] [PubMed]
  113. Sun, F.; Wang, T.; Jiang, J.; Wang, Y.; Ma, Z.; Li, Z.; Han, Y.; Pan, M.; Cai, J.; Wang, M.; et al. Engineering a high-affinity humanized anti-CD24 antibody to target hepatocellular carcinoma by a novel CDR grafting design. Oncotarget 2017, 8, 51238–51252. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  114. Ma, Z.; He, H.; Sun, F.; Xu, Y.; Huang, X.; Ma, Y.; Zhao, H.; Wang, Y.; Wang, M.; Zhang, J. Selective targeted delivery of doxorubicin via conjugating to anti-CD24 antibody results in enhanced antitumor potency for hepatocellular carcinoma both in vitro and in vivo. J. Cancer Res. Clin. Oncol. 2017, 143, 1929–1940. [Google Scholar] [CrossRef] [PubMed]
  115. Sun, F.; Wang, Y.; Luo, X.; Ma, Z.; Xu, Y.; Zhang, X.; Lv, T.; Zhang, Y.; Wang, M.; Huang, Z.; et al. Anti-CD24 Antibody-Nitric Oxide Conjugate Selectively and Potently Suppresses Hepatic Carcinoma. Cancer Res. 2019, 79, 3395–3405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  116. Maliar, A.; Servais, C.; Waks, T.; Chmielewski, M.; Lavy, R.; Altevogt, P.; Abken, H.; Eshhar, Z. Redirected T cells that target pancreatic adenocarcinoma antigens eliminate tumors and metastases in mice. Gastroenterology 2012, 143, 1375–1384.e5. [Google Scholar] [CrossRef]
  117. Wu, H.; Liu, J.; Wang, Z.; Yuan, W.; Chen, L. Prospects of antibodies targeting CD47 or CD24 in the treatment of glioblastoma. CNS Neurosci. Ther. 2021, 27, 1105–1117. [Google Scholar] [CrossRef]
  118. Han, Y.; Sun, F.; Zhang, X.; Wang, T.; Jiang, J.; Cai, J.; Gao, Q.; Hezam, K.; Liu, Y.; Xie, J.; et al. CD24 targeting bi-specific antibody that simultaneously stimulates NKG2D enhances the efficacy of cancer immunotherapy. J. Cancer Res. Clin. Oncol. 2019, 145, 1179–1190. [Google Scholar] [CrossRef]
  119. Lu, R.-M.; Hwang, Y.-C.; Liu, I.-J.; Lee, C.-C.; Tsai, H.-Z.; Li, H.-J.; Wu, H.-C. Development of therapeutic antibodies for the treatment of diseases. J. Biomed. Sci. 2020, 27, 1. [Google Scholar] [CrossRef] [PubMed]
  120. Brentuximab Vedotin. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/brentuximab-vedotin (accessed on 4 April 2022).
  121. June, C.H.; O’Connor, R.S.; Kawalekar, O.U.; Ghassemi, S.; Milone, M.C. CAR T cell immunotherapy for human cancer. Science 2018, 359, 1361–1365. [Google Scholar] [CrossRef] [Green Version]
  122. Klapdor, R.; Wang, S.; Morgan, M.; Dörk, T.; Hacker, U.; Hillemanns, P.; Büning, H.; Schambach, A. Characterization of a Novel Third-Generation Anti-CD24-CAR against Ovarian Cancer. Int. J. Mol. Sci. 2019, 20, 660. [Google Scholar] [CrossRef] [Green Version]
  123. Cioca, D.P.; Deak, E.; Cioca, F.; Paunescu, V. Monoclonal antibodies targeted against melanoma and ovarian tumors enhance dendritic cell-mediated cross-presentation of tumor-associated antigens and efficiently cross-prime CD8+ T cells. J. Immunother. Hagerstown Md 1997 2006, 29, 41–52. [Google Scholar] [CrossRef] [PubMed]
  124. Fischer, A.; Blanche, S.; Le Bidois, J.; Bordigoni, P.; Garnier, J.L.; Niaudet, P.; Morinet, F.; Le Deist, F.; Fischer, A.-M.; Griscelli, C.; et al. Anti–B-Cell Monoclonal Antibodies in the Treatment of Severe B-Cell Lymphoproliferative Syndrome Following Bone Marrow and Organ Transplantation. N. Engl. J. Med. 1991, 324, 1451–1456. [Google Scholar] [CrossRef]
  125. Benkerrou, M.; Jais, J.-P.; Leblond, V.; Durandy, A.; Sutton, L.; Bordigoni, P.; Garnier, J.L.; Le Bidois, J.; Le Deist, F.; Blanche, S.; et al. Anti–B-Cell Monoclonal Antibody Treatment of Severe Posttransplant B-Lymphoproliferative Disorder: Prognostic Factors and Long-Term Outcome. Blood 1998, 92, 3137–3147. [Google Scholar] [CrossRef] [PubMed]
  126. National Comprehensive Cancer Network B-Cell Lymphomas (Version 2.2022). Available online: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf (accessed on 23 March 2022).
  127. Xu, K.; Meng, Z.; Mu, X.; Sun, B.; Chai, Y. One Single Site Clinical Study: To Evaluate the Safety and Efficacy of Immunotherapy with Autologous Dendritic Cells, Cytokine-Induced Killer Cells in Primary Hepatocellular Carcinoma Patients. Front. Oncol. 2020, 10, 581270. [Google Scholar] [CrossRef]
  128. Toubai, T.; Rossi, C.; Oravecz-Wilson, K.; Zajac, C.; Liu, C.; Braun, T.; Fujiwara, H.; Wu, J.; Sun, Y.; Brabbs, S.; et al. Siglec-G represses DAMP-mediated effects on T cells. JCI Insight 2017, 2, e92293. [Google Scholar] [CrossRef] [Green Version]
Table
Table 1. Association between CD24 overexpression and disease features across different tumor types.
Table 1. Association between CD24 overexpression and disease features across different tumor types.
Tumor TypeCD24 OverexpressionDisease CharacteristicsOutcomeReference
Hepatocellular
carcinoma		High IHC expressionNADecreased OS[27]
Breast carcinomaModerate/high-intensity IHC staining or present in >26% of cellsLuminal A subtypeDecreased OS[29]
Breast carcinomamRNA expression
>median		TNBC subtypeDecreased OS[30]
Ovarian carcinomamRNA expression
>median		NADecreased RFS[30]
Colorectal
adenocarcinoma		Moderate/high IHC staining, mRNA expression >90th percentileNAIncreased OS[42]
Urothelial carcinomaModerate/high-intensity IHC staining in >10% of cellsHigh grade, stageNA[43]
Prostate
adenocarcinoma		Any IHC stainingHigh stageDecreased PSA relapse time[35]
Oral squamous
cell carcinoma		IHC staining in >10% of cellsNADecreased ORR to neoadjuvant therapy[36]
Multiple myelomaBM PC expression >5% by flow cytometryNAIncreased PFS, OS[41]
Abbreviations—BM: bone marrow, CRC: colorectal carcinoma, HCC: hepatocellular carcinoma, IHC: immunohistochemistry, ORR: objective response rate, OS: overall survival, PC: plasma cell, PFS: progression-free survival, RFS: relapse-free survival.
Table
Table 2. Effects of CD24 signaling different subtypes of immune cells.
Table 2. Effects of CD24 signaling different subtypes of immune cells.
Immune Cell SubypeEffectProposed MechanismOutcome
T cellsRegulation of proliferationInhibition of rapid T cell proliferation in lymphopenic hostsInhibition
T cellsDownregulation of Th1, upregulation of Treg cellsCD24+ Breg cellsInhibition
T cellsPromotion of the differentiation of memory/effector T cellsCostimulatory signal for naive CD8+ T cellsActivation
NK cellsReduced NK cell cytotoxicitySiglec-10-mediatedInhibition
MacrophagesInhibition of phagocytosisSiglec-10-mediatedInhibition
Monocytes/neutrophilsHematogenous spreadP-selectin-mediated cell adhesion to activated endothelial cells or plateletsActivation
Dendritic cellsSuppression of immune response to tissue damageInhibition of TLR-mediated inflammation via Siglec-10 interactionInhibition
Table
Table 3. Preclinical studies in vivo with agents that target CD24.
Table 3. Preclinical studies in vivo with agents that target CD24.
Tumor TypeAnti-CD24 AgentOther AgentsResultProposed
Mechanism		Reference
Urothelial carcinomaALB9NATumor growth inhibitionInhibition of P-selectin-mediated metastatic dissemination[34]
Lung adenocarcinomaSWA11NATumor growth inhibitionInhibition of Src/STAT3 signaling[21]
Pancreatic adenocarcinomaSWA11NATumor growth inhibitionInhibition of Src/STAT3 signaling
Ovarian carcinomaSWA11NATumor growth inhibitionInhibition of Src/STAT3 signaling
Lung adenocarcinomaSWA11GemcitabineTumor growth inhibition, increased efficacy of gemcitabineModification of intratumoral cytokine microenvironment[105]
Ovarian carcinomaSWA11NATumor growth inhibitionModification of intratumoral cytokine microenvironment
Colorectal adenocarcinomaSWA11Paclitaxel, doxorubicin, 5-fluorouracil, oxaliplatin, irinotecanTumor growth inhibition, increased efficacy of chemotherapeutic agentsInhibition of Ras pathway[106]
Breast carcinomaSN3NATumor growth inhibitionPromotion of phagocytosis by Siglec-10-expressing macrophages[30]
Lung adenocarcinomaG7mAbCetuximabImproved survivalInhibition of STAT3 signaling by dual targeting of CD24 and EGFR[107]
Hepatocellular carcinomaG7mAbCetuximabTumor growth inhibition, improved survivalInhibition of STAT3 signaling by dual targeting of CD24 and EGFR
Colorectal adenocarcinomaG7mAbCetuximabTumor growth inhibition, improved survivalInhibition of STAT3 signaling by dual targeting of CD24 and EGFR
Hepatocellular carcinomarG7S-MICANATumor growth inhibitionNK cell recruitment through MICA/NKG2D pathway[108]
Breast carcinomascFvsEpirubicinTumor growth inhibition, increased efficacy of epirubicinTargeting of CD44+/CD24+ cells[109]
Small cell lung cancerSWA11-SPDB-dg.ricin A chainNATumor growth inhibitionTargeted, ricin-mediated toxicity[110]
Burkitt’s lymphomaSWA11.dgANADurable complete remissionsTargeted, ricin-mediated toxicity[111]
Colorectal adenocarcinomaSWA11-ZZ-PE38NATumor growth inhibitionTargeted, exotoxin-mediated cytotoxicity[112]
Hepatocellular carcinomahG7-BM3-VcMMNATumor growth inhibitionTargeted, MMAE-mediated cytotoxicity[113]
Hepatocellular carcinomaG7mAb-DOXNATumor growth inhibition, improved survivalTargeted, doxorubicin-mediated cytotoxicity[114]
Hepatocellular carcinomaHN-01NATumor growth inhibition, improved survivalTargeted, intracellular release of nitric oxide[115]
Pancreatic adenocarcinomaCAR-redirected anti-CD24 T-cellsNATumor growth inhibition, improved survivalT-cell mediated cytotoxicity[116]
Table
Table 4. Clinical trials with agents targeting CD24 in patients with cancer.
Table 4. Clinical trials with agents targeting CD24 in patients with cancer.
Trial IdentifierInclusionAgentPhaseSettingPrimary OutcomeEnrollmentStatusResults
NCT04552704Advanced Solid TumorsCD24 agonistI/IIAnySafety, tolerability, recovery from irAEs78Active, not recruitingNo
NCT04060407Unresectable or metastatic melanomaCD24 agonist, nivolumab, ipilimumabIb/IIAnySafety, tolerability0WithdrawnNo
NAPosttransplant BLPDALB9, BL13I/IIFirst lineSafety, tolerability58CompletedYes
NAResected HCCCD24-loaded DC/CIK autotransfusionI/IIAdjuvantSafety, efficacy36CompletedYes
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Panagiotou, E.; Syrigos, N.K.; Charpidou, A.; Kotteas, E.; Vathiotis, I.A. CD24: A Novel Target for Cancer Immunotherapy. J. Pers. Med. 2022, 12, 1235. https://doi.org/10.3390/jpm12081235

AMA Style

Panagiotou E, Syrigos NK, Charpidou A, Kotteas E, Vathiotis IA. CD24: A Novel Target for Cancer Immunotherapy. Journal of Personalized Medicine. 2022; 12(8):1235. https://doi.org/10.3390/jpm12081235

Chicago/Turabian Style

Panagiotou, Emmanouil, Nikolaos K. Syrigos, Andriani Charpidou, Elias Kotteas, and Ioannis A. Vathiotis. 2022. "CD24: A Novel Target for Cancer Immunotherapy" Journal of Personalized Medicine 12, no. 8: 1235. https://doi.org/10.3390/jpm12081235

APA Style

Panagiotou, E., Syrigos, N. K., Charpidou, A., Kotteas, E., & Vathiotis, I. A. (2022). CD24: A Novel Target for Cancer Immunotherapy. Journal of Personalized Medicine, 12(8), 1235. https://doi.org/10.3390/jpm12081235

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop