Biomedicines

Research

13 pages, 2603 KiB

Open AccessArticle

Impact of Liver Metastases and Number of Metastatic Sites on Immune-Checkpoint Inhibitors Efficacy in Patients with Different Solid Tumors: A Retrospective Study

by Madeleine Maugeais, Julien Péron, Stéphane Dalle, Amélie Boespflug, Michaël Duruissaux, Pauline Corbaux, Thibault Reverdy, Gulsum Sahin, Aurélie Rabier, Jonathan Lopez, Nathalie Freymond and Denis Maillet

Biomedicines 2023, 11(1), 83; https://doi.org/10.3390/biomedicines11010083 - 29 Dec 2022

Cited by 5 | Viewed by 2005

Abstract

Background: ICIs have dramatically improved patient outcomes in different malignancies. However, the impact of liver metastases (LM) and number of metastatic sites (MS) remains unclear in patients treated with single-agent anti-PD(L)1. Methods: We aimed to assess the prognostic impact of LM and MS [...] Read more.

Background: ICIs have dramatically improved patient outcomes in different malignancies. However, the impact of liver metastases (LM) and number of metastatic sites (MS) remains unclear in patients treated with single-agent anti-PD(L)1. Methods: We aimed to assess the prognostic impact of LM and MS number on progression-free survival (PFS) and overall survival (OS) in a large single-arm retrospective multicentric cohort (IMMUCARE) of patients treated with anti-PD(L)-1 for different solid tumors. Results: A total of 759 patients were enrolled from January 2012 to October 2018. The primary tumor types were non-small cell lung cancer (71%), melanoma (19%), or urologic cancer (10%). At the time of ICI initiation, 167 patients (22%) had LM and 370 patients (49%) had more than MS. LM was associated with a shorter median PFS of 1.9 months (95% CI: 1.8–2.5) vs. 4.0 months (95% CI: 3.6–5.4) in patients without LM (p < 0.001). The median OS of patients with LM was of 5.2 months (95% CI: 4.0–7.7) compared with 12.8 months (95% CI: 11.2–15.1) (p < 0.001). Interestingly, LM were not associated with shorter PFS, or OS compared to other MS types (brain, bone, or lung) in patients with only one MS. Patients with multiple MS also had poor clinical outcomes compared to patients with only one MS. The presence of LM and MS number were independent prognostic factors on overall survival. Conclusion: The presence of LM or multiple MS were associated with poorer survival outcomes in patients treated with anti-PD(L)-1. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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17 pages, 2573 KiB

Open AccessArticle

Prevention and Therapy of Metastatic HER-2⁺ Mammary Carcinoma with a Human Candidate HER-2 Virus-like Particle Vaccine

by Francesca Ruzzi, Arianna Palladini, Stine Clemmensen, Anette Strøbæk, Nicolaas Buijs, Tanja Domeyer, Jerzy Dorosz, Vladislav Soroka, Dagmara Grzadziela, Christina Jo Rasmussen, Ida Busch Nielsen, Max Soegaard, Maria Sofia Semprini, Laura Scalambra, Stefania Angelicola, Lorena Landuzzi, Pier-Luigi Lollini and Mette Thorn

Biomedicines 2022, 10(10), 2654; https://doi.org/10.3390/biomedicines10102654 - 20 Oct 2022

Cited by 2 | Viewed by 4763

Abstract

Vaccines are a promising therapeutic alternative to monoclonal antibodies against HER-2⁺ breast cancer. We present the preclinical activity of an ES2B-C001, a VLP-based vaccine being developed for human breast cancer therapy. FVB mice challenged with HER-2⁺ mammary carcinoma cells QD developed [...] Read more.

Vaccines are a promising therapeutic alternative to monoclonal antibodies against HER-2⁺ breast cancer. We present the preclinical activity of an ES2B-C001, a VLP-based vaccine being developed for human breast cancer therapy. FVB mice challenged with HER-2⁺ mammary carcinoma cells QD developed progressive tumors, whereas all mice vaccinated with ES2B-C001+Montanide ISA 51, and 70% of mice vaccinated without adjuvant, remained tumor-free. ES2B-C001 completely inhibited lung metastases in mice challenged intravenously. HER-2 transgenic Delta16 mice developed mammary carcinomas by 4–8 months of age; two administrations of ES2B-C001+Montanide prevented tumor onset for >1 year. Young Delta16 mice challenged intravenously with QD cells developed a mean of 68 lung nodules in 13 weeks, whereas all mice vaccinated with ES2B-C001+Montanide, and 73% of mice vaccinated without adjuvant, remained metastasis-free. ES2B-C001 in adjuvant elicited strong anti-HER-2 antibody responses comprising all Ig isotypes; titers ranging from 1–10 mg/mL persisted for many months. Antibodies inhibited the 3D growth of human HER-2⁺ trastuzumab-sensitive and -resistant breast cancer cells. Vaccination did not induce cytokine storms; however, it increased the ELISpot frequency of IFN-γ secreting HER-2-specific splenocytes. ES2B-C001 is a promising candidate vaccine for the therapy of tumors expressing HER-2. Preclinical results warrant further development towards human clinical studies. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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12 pages, 2084 KiB

Open AccessArticle

Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients

by Hilde Haave, Borghild Ljokjel, Helene Lybak, Svein E. Moe, Jan E. Berge, Olav K. Vintermyr, Lars Helgeland and Hans J. Aarstad

Biomedicines 2022, 10(10), 2484; https://doi.org/10.3390/biomedicines10102484 - 5 Oct 2022

Cited by 5 | Viewed by 1521

Abstract

Oropharynx squamous cell carcinoma (OPSCC) is of special interest because human papilloma virus (HPV) and/or smoking cause this disease. Influxes of inflammatory cells into such tumors are known to vary with prognoses. Aims: To study whether the density of tumor-infiltrating T lymphocytes and [...] Read more.

Oropharynx squamous cell carcinoma (OPSCC) is of special interest because human papilloma virus (HPV) and/or smoking cause this disease. Influxes of inflammatory cells into such tumors are known to vary with prognoses. Aims: To study whether the density of tumor-infiltrating T lymphocytes and tumor-infiltrating macrophages predicted general 20-year overall survival (OS), as well as OS with only disease-specific survival (DSS) patients included. Methods: Biopsies from patients treated for OPSCC (n = 180) were stained by immunohistochemistry and the tumor cell macrophage (CD68), pan T lymphocytes (CD3), and regulatory T lymphocytes (Foxp3) densities were determined. The HE-determined percentage of matured tumor cells and the rate of invasion were calculated, and stromal desmoplasia were performed. Tumor HPV presence was studied by PCR. Twenty-year OS and five-year DSS patients were determined. Results: Tumor HPV status strongly predicted survival. High tumor infiltration of CD3, Foxp3 and CD68-positive cells predicted better twenty-year OS, with and without HPV stratification. Foxp3 and CD68 levels predicted OS, and 20-year among DSS patients, primarily among HPV(+) patients. Tumor HE-derived variables did not predict such survival. Conclusions: Tumor HPV status, level of Foxp3 tumor-infiltrating lymphocytes and CD68 tumor-infiltrating macrophages predicted up to 20-year OS of both all patients and disease-specific survived patients. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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16 pages, 3642 KiB

Open AccessArticle

Biomarkers for Immunotherapy in Poorly Differentiated Sinonasal Tumors

by Eva Villanueva-Fernández, Mario A. Hermsen, Laura Suárez-Fernández, Blanca Vivanco, Alessandro Franchi, Rocío García-Marín, Virginia N. Cabal, Helena Codina-Martínez, Sara Lucila Lorenzo-Guerra, José L. Llorente and Fernando López

Biomedicines 2022, 10(9), 2205; https://doi.org/10.3390/biomedicines10092205 - 6 Sep 2022

Cited by 7 | Viewed by 2046

Abstract

The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low. Thus, there is an unmet clinical need for [...] Read more.

The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low. Thus, there is an unmet clinical need for new therapeutic options. We retrospectively evaluated poorly differentiated tumors of 9 different histological subtypes from 69 patients who had received conventional treatments for the presence of CD8+ tumor-infiltrating lymphocytes (TILs), as well as the expression of PD-L1 and microsatellite instability (MSI) markers MLH1, MSH2, MSH6 and PMS2, as biomarkers for immunotherapy. CD8+ TILs were present in 23/69 (33%) cases, PD-L1 expression was observed in 23/69 (33%), and markers for MSI positivity in 5/69 (7%) cases. CD8+ TILs correlated with PD-L1 positivity, while both were mutually exclusive with MSI markers. None of the biomarkers were associated with clinical features as age, gender or tumor stage. Cases with CD8+ TILs and PD-L1 positivity showed a tendency toward worse disease-specific survival. Immune checkpoint inhibitors are emerging as new options for treatment of many tumor types. Our results indicate that also a substantial subset of patients with poorly differentiated sinonasal tumors may be a candidate to be treated with this promising new therapy. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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17 pages, 5925 KiB

Open AccessArticle

The Generation of Dual-Targeting Fusion Protein PD-L1/CD47 for the Inhibition of Triple-Negative Breast Cancer

by Yanlin Bian, Tong Lin, Tanja Jakos, Xiaodong Xiao and Jianwei Zhu

Biomedicines 2022, 10(8), 1843; https://doi.org/10.3390/biomedicines10081843 - 30 Jul 2022

Cited by 3 | Viewed by 3062

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subset of breast cancer with limited therapeutic options. However, its immune evasion mechanisms, characterized by the over-expression of the immune checkpoint molecules PD-L1 and CD47, can be targeted in order to facilitate cancer elimination by [...] Read more.

Triple-negative breast cancer (TNBC) is a highly aggressive subset of breast cancer with limited therapeutic options. However, its immune evasion mechanisms, characterized by the over-expression of the immune checkpoint molecules PD-L1 and CD47, can be targeted in order to facilitate cancer elimination by cells of innate and adaptive immunity. In this paper, we describe the design, preparation, and evaluation of three novel dual-targeting fusion proteins that were based on the structure frame of prototype IAB (innate and adaptive dependent bispecific fusion protein) and the “Orcutt-type IgG-scFv” molecular model. Three molecules with different spatial conformations were designed to improve antigen–antibody affinity by the addition of Ag–Ab binding sites from the variable region sequences of the anti-PD-L1 monoclonal antibody (mAb) atezolizumab and CV1, a high-affinity receptor of CD47. The results showed that the best-performing among the three proteins designed in this study was protein Pro3; its CV1 N-terminus and Fc domain C-terminus were not sterically hindered. Pro3 was better at boosting T cell proliferation and the engulfment of macrophages than the IAB prototype and, at the same time, retained a level of ADCC activity similar to that of IAB. Through improved design, the novel constructed dual-targeting immunomodulatory protein Pro3 was superior at activating the anti-tumor immune response and has thus shown potential for use in clinical applications. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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19 pages, 3379 KiB

Open AccessArticle

CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma

by Jimena Álvarez Freile, Natasha Ustyanovska Avtenyuk, Macarena González Corrales, Harm Jan Lourens, Gerwin Huls, Tom van Meerten, Ewa Cendrowicz and Edwin Bremer

Biomedicines 2022, 10(5), 1175; https://doi.org/10.3390/biomedicines10051175 - 19 May 2022

Cited by 23 | Viewed by 4025

Abstract

CD24 and its ligand Siglec-10 were described as an innate immune checkpoint in carcinoma. Here, we investigated this axis in B-cell lymphoma by assessing CD24 expression and evaluating pro-phagocytic effects of CD24 antibody treatment in comparison to hallmark immune checkpoint CD47. In mantle [...] Read more.

CD24 and its ligand Siglec-10 were described as an innate immune checkpoint in carcinoma. Here, we investigated this axis in B-cell lymphoma by assessing CD24 expression and evaluating pro-phagocytic effects of CD24 antibody treatment in comparison to hallmark immune checkpoint CD47. In mantle cell lymphoma (MCL) and follicular lymphoma patients, high mRNA expression of CD24 correlated with poor overall survival, whereas CD47 expression did not. Conversely, CD24 expression did not correlate with survival in diffuse large B-cell lymphoma (DLBCL), whereas CD47 did. CD24 was also highly expressed on MCL cell lines, where treatment with CD24 antibody clones SN3 or ML5 potently induced phagocytosis, with SN3 yielding >90% removal of MCL cells and triggering phagocytosis of primary patient-derived MCL cells by autologous macrophages. Treatment with CD24 mAb was superior to CD47 mAb in MCL and was comparable in magnitude to the effect observed in carcinoma lines. Reversely, CD24 mAb treatment was less effective than CD47 mAb treatment in DLBCL. Finally, phagocytic activity of clone SN3 appeared at least partly independent of antibody-dependent cellular phagocytosis (ADCP), suggesting CD24/Siglec-10 checkpoint activity, whereas clone ML5 solely induced ADCP. In conclusion, CD24 is an immunotherapeutic target of potential clinical relevance for MCL, but not DLBCL. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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Review

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37 pages, 3592 KiB

Open AccessReview

Small Molecule Targeting Immune Cells: A Novel Approach for Cancer Treatment

by Shilpi Singh, Debashis Barik, Ananta Prasad Arukha, Sujata Prasad, Iteeshree Mohapatra, Amar Singh and Gatikrushna Singh

Biomedicines 2023, 11(10), 2621; https://doi.org/10.3390/biomedicines11102621 - 24 Sep 2023

Cited by 7 | Viewed by 4113

Abstract

Conventional and cancer immunotherapies encompass diverse strategies to address various cancer types and stages. However, combining these approaches often encounters limitations such as non-specific targeting, resistance development, and high toxicity, leading to suboptimal outcomes in many cancers. The tumor microenvironment (TME) is orchestrated [...] Read more.

Conventional and cancer immunotherapies encompass diverse strategies to address various cancer types and stages. However, combining these approaches often encounters limitations such as non-specific targeting, resistance development, and high toxicity, leading to suboptimal outcomes in many cancers. The tumor microenvironment (TME) is orchestrated by intricate interactions between immune and non-immune cells dictating tumor progression. An innovative avenue in cancer therapy involves leveraging small molecules to influence a spectrum of resistant cell populations within the TME. Recent discoveries have unveiled a phenotypically diverse cohort of innate-like T (ILT) cells and tumor hybrid cells (HCs) exhibiting novel characteristics, including augmented proliferation, migration, resistance to exhaustion, evasion of immunosurveillance, reduced apoptosis, drug resistance, and heightened metastasis frequency. Leveraging small-molecule immunomodulators to target these immune players presents an exciting frontier in developing novel tumor immunotherapies. Moreover, combining small molecule modulators with immunotherapy can synergistically enhance the inhibitory impact on tumor progression by empowering the immune system to meticulously fine-tune responses within the TME, bolstering its capacity to recognize and eliminate cancer cells. This review outlines strategies involving small molecules that modify immune cells within the TME, potentially revolutionizing therapeutic interventions and enhancing the anti-tumor response. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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24 pages, 900 KiB

Open AccessReview

A Holistic Approach to Hard-to-Treat Cancers: The Future of Immunotherapy for Glioblastoma, Triple Negative Breast Cancer, and Advanced Prostate Cancer

by Carles Puig-Saenz, Joshua R. D. Pearson, Jubini E. Thomas and Stéphanie E. B. McArdle

Biomedicines 2023, 11(8), 2100; https://doi.org/10.3390/biomedicines11082100 - 25 Jul 2023

Cited by 2 | Viewed by 2574

Abstract

Immunotherapy represents an attractive avenue for cancer therapy due to its tumour specificity and relatively low frequency of adverse effects compared to other treatment modalities. Despite many advances being made in the field of cancer immunotherapy, very few immunotherapeutic treatments have been approved [...] Read more.

Immunotherapy represents an attractive avenue for cancer therapy due to its tumour specificity and relatively low frequency of adverse effects compared to other treatment modalities. Despite many advances being made in the field of cancer immunotherapy, very few immunotherapeutic treatments have been approved for difficult-to-treat solid tumours such as triple negative breast cancer (TNBC), glioblastoma multiforme (GBM), and advanced prostate cancer (PCa). The anatomical location of some of these cancers may also make them more difficult to treat. Many trials focus solely on immunotherapy and have failed to consider or manipulate, prior to the immunotherapeutic intervention, important factors such as the microbiota, which itself is directly linked to lifestyle factors, diet, stress, social support, exercise, sleep, and oral hygiene. This review summarises the most recent treatments for hard-to-treat cancers whilst factoring in the less conventional interventions which could tilt the balance of treatment in favour of success for these malignancies. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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24 pages, 3121 KiB

Open AccessReview

Nanomaterials for Skin Cancer Photoimmunotherapy

by Carlota M. Relvas, Susana G. Santos, Maria J. Oliveira, Fernão D. Magalhães and Artur M. Pinto

Biomedicines 2023, 11(5), 1292; https://doi.org/10.3390/biomedicines11051292 - 27 Apr 2023

Cited by 2 | Viewed by 2330

Abstract

Skin cancer is one of the most common types of cancer, and its incidence continues to increase. It is divided into two main categories, melanoma and non-melanoma. Treatments include surgery, radiation therapy, and chemotherapy. The relatively high mortality in melanoma and the existing [...] Read more.

Skin cancer is one of the most common types of cancer, and its incidence continues to increase. It is divided into two main categories, melanoma and non-melanoma. Treatments include surgery, radiation therapy, and chemotherapy. The relatively high mortality in melanoma and the existing recurrence rates, both for melanoma and non-melanoma, create the need for studying and developing new approaches for skin cancer management. Recent studies have focused on immunotherapy, photodynamic therapy, photothermal therapy, and photoimmunotherapy. Photoimmunotherapy has gained much attention due to its excellent potential outcomes. It combines the advantages of photodynamic and/or photothermal therapy with a systemic immune response, making it ideal for metastatic cancer. This review critically discusses different new nanomaterials’ properties and mechanisms of action for skin cancer photoimmunotherapy and the main results obtained in the field. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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14 pages, 349 KiB

Open AccessReview

Wnt/β-Catenin Signaling and Resistance to Immune Checkpoint Inhibitors: From Non-Small-Cell Lung Cancer to Other Cancers

by Satoshi Muto, Akio Enta, Yoshiyuki Maruya, Sho Inomata, Hikaru Yamaguchi, Hayato Mine, Hironori Takagi, Yuki Ozaki, Masayuki Watanabe, Takuya Inoue, Takumi Yamaura, Mitsuro Fukuhara, Naoyuki Okabe, Yuki Matsumura, Takeo Hasegawa, Jun Osugi, Mika Hoshino, Mitsunori Higuchi, Yutaka Shio, Kazuyuki Hamada and Hiroyuki Suzuki Show full author list Hide full author list

Biomedicines 2023, 11(1), 190; https://doi.org/10.3390/biomedicines11010190 - 12 Jan 2023

Cited by 16 | Viewed by 4233

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. The standard of care for advanced non-small-cell lung cancer (NSCLC) without driver-gene mutations is a combination of an anti-PD-1/PD-L1 antibody and chemotherapy, or an anti-PD-1/PD-L1 antibody and an anti-CTLA-4 antibody with or without [...] Read more.

Lung cancer is the leading cause of cancer-related deaths worldwide. The standard of care for advanced non-small-cell lung cancer (NSCLC) without driver-gene mutations is a combination of an anti-PD-1/PD-L1 antibody and chemotherapy, or an anti-PD-1/PD-L1 antibody and an anti-CTLA-4 antibody with or without chemotherapy. Although there were fewer cases of disease progression in the early stages of combination treatment than with anti-PD-1/PD-L1 antibodies alone, only approximately half of the patients had a long-term response. Therefore, it is necessary to elucidate the mechanisms of resistance to immune checkpoint inhibitors. Recent reports of such mechanisms include reduced cancer-cell immunogenicity, loss of major histocompatibility complex, dysfunctional tumor-intrinsic interferon-γ signaling, and oncogenic signaling leading to immunoediting. Among these, the Wnt/β-catenin pathway is a notable potential mechanism of immune escape and resistance to immune checkpoint inhibitors. In this review, we will summarize findings on these resistance mechanisms in NSCLC and other cancers, focusing on Wnt/β-catenin signaling. First, we will review the molecular biology of Wnt/β-catenin signaling, then discuss how it can induce immunoediting and resistance to immune checkpoint inhibitors. We will also describe other various mechanisms of immune-checkpoint-inhibitor resistance. Finally, we will propose therapeutic approaches to overcome these mechanisms. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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17 pages, 1841 KiB

Open AccessFeature PaperReview

Cutting-Edge CAR Engineering: Beyond T Cells

by Luisa Chocarro, Ester Blanco, Leticia Fernández-Rubio, Hugo Arasanz, Ana Bocanegra, Miriam Echaide, Maider Garnica, Pablo Ramos, Sergio Piñeiro-Hermida, Ruth Vera, Grazyna Kochan and David Escors

Biomedicines 2022, 10(12), 3035; https://doi.org/10.3390/biomedicines10123035 - 24 Nov 2022

Cited by 7 | Viewed by 3314

Abstract

Chimeric antigen receptor (CAR)-T adoptive cell therapy is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in haematological malignancies. However, it still lacks efficacy in solid tumours, possibly because engineered T cells become inactive within the [...] Read more.

Chimeric antigen receptor (CAR)-T adoptive cell therapy is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in haematological malignancies. However, it still lacks efficacy in solid tumours, possibly because engineered T cells become inactive within the immunosuppressive tumour microenvironment (TME). In the TME, cells of the myeloid lineage (M) are among the immunosuppressive cell types with the highest tumour infiltration rate. These cells interact with other immune cells, mediating immunosuppression and promoting angiogenesis. Recently, the development of CAR-M cell therapies has been put forward as a new candidate immunotherapy with good efficacy potential. This alternative CAR strategy may increase the efficacy, survival, persistence, and safety of CAR treatments in solid tumours. This remains a critical frontier in cancer research and opens up a new possibility for next-generation personalised medicine to overcome TME resistance. However, the exact mechanisms of action of CAR-M and their effect on the TME remain poorly understood. Here, we summarise the basic, translational, and clinical results of CAR-innate immune cells and CAR-M cell immunotherapies, from their engineering and mechanistic studies to preclinical and clinical development. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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18 pages, 811 KiB

Open AccessReview

Endoscopic Applications of Near-Infrared Photoimmunotherapy (NIR-PIT) in Cancers of the Digestive and Respiratory Tracts

by Hideyuki Furumoto, Takuya Kato, Hiroaki Wakiyama, Aki Furusawa, Peter L. Choyke and Hisataka Kobayashi

Biomedicines 2022, 10(4), 846; https://doi.org/10.3390/biomedicines10040846 - 4 Apr 2022

Cited by 5 | Viewed by 4014

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and promising therapy that specifically destroys target cells by irradiating antibody-photo-absorber conjugates (APCs) with NIR light. APCs bind to target molecules on the cell surface, and when exposed to NIR light, cause disruption of the cell [...] Read more.

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and promising therapy that specifically destroys target cells by irradiating antibody-photo-absorber conjugates (APCs) with NIR light. APCs bind to target molecules on the cell surface, and when exposed to NIR light, cause disruption of the cell membrane due to the ligand release reaction and dye aggregation. This leads to rapid cell swelling, blebbing, and rupture, which leads to immunogenic cell death (ICD). ICD activates host antitumor immunity, which assists in killing still viable cancer cells in the treated lesion but is also capable of producing responses in untreated lesions. In September 2020, an APC and laser system were conditionally approved for clinical use in unresectable advanced head and neck cancer in Japan, and are now routine in appropriate patients. However, most tumors have been relatively accessible in the oral cavity or neck. Endoscopes offer the opportunity to deliver light deeper within hollow organs of the body. In recent years, the application of endoscopic therapy as an alternative to surgery for the treatment of cancer has expanded, providing significant benefits to inoperable patients. In this review, we will discuss the potential applications of endoscopic NIR-PIT, especially in thoracic and gastrointestinal cancers. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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19 pages, 1287 KiB

Open AccessReview

Assessing the Future of Solid Tumor Immunotherapy

by Prajna Guha, Kara R. Heatherton, Kyle P. O’Connell, Ian S. Alexander and Steven C. Katz

Biomedicines 2022, 10(3), 655; https://doi.org/10.3390/biomedicines10030655 - 11 Mar 2022

Cited by 51 | Viewed by 6570

Abstract

With the advent of cancer immunotherapy, there has been a major improvement in patient’s quality of life and survival. The growth of cancer immunotherapy has dramatically changed our understanding of the basics of cancer biology and has altered the standards of care (surgery, [...] Read more.

With the advent of cancer immunotherapy, there has been a major improvement in patient’s quality of life and survival. The growth of cancer immunotherapy has dramatically changed our understanding of the basics of cancer biology and has altered the standards of care (surgery, radiotherapy, and chemotherapy) for patients. Cancer immunotherapy has generated significant excitement with the success of chimeric antigen receptor (CAR) T cell therapy in particular. Clinical results using CAR-T for hematological malignancies have led to the approval of four CD19-targeted and one B-cell maturation antigen (BCMA)-targeted cell therapy products by the US Food and Drug Administration (FDA). Also, immune checkpoint inhibitors such as antibodies against Programmed Cell Death-1 (PD-1), Programmed Cell Death Ligand-1 (PD-L1), and Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4) have shown promising therapeutic outcomes and long-lasting clinical effect in several tumor types and patients who are refractory to other treatments. Despite these promising results, the success of cancer immunotherapy in solid tumors has been limited due to several barriers, which include immunosuppressive tumor microenvironment (TME), inefficient trafficking, and heterogeneity of tumor antigens. This is further compounded by the high intra-tumoral pressure of solid tumors, which presents an additional challenge to successfully delivering treatments to solid tumors. In this review, we will outline and propose specific approaches that may overcome these immunological and physical barriers to improve the outcomes in solid tumor patients receiving immunotherapies. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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20 pages, 2819 KiB

Open AccessSystematic Review

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis

by Omar Fahmy, Osama A. A. Ahmed, Mohd Ghani Khairul-Asri, Nabil A. Alhakamy, Waleed S. Alharbi, Usama A. Fahmy, Mohamed A. El-Moselhy, Claudia G. Fresta, Giuseppe Caruso and Filippo Caraci

Biomedicines 2022, 10(5), 1101; https://doi.org/10.3390/biomedicines10051101 - 10 May 2022

Cited by 5 | Viewed by 2289

Abstract

Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of [...] Read more.

Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. Methods: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. Results: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p < 0.00001; RR = 1.91), rash incidence was equal to 11.1% (160/1441) vs. 6.5% (86/1320) (Z = 4.35; p <0.0001; RR = 1.75), pruritis was 13.6% (201/1473) vs. 7.7% (104/1352) (Z = 5.35; p < 0.00001; RR = 1.83), fever was 10.5% (42/399) vs. 6.6% (22/330) (Z = 2.27; p = 0.02; RR = 1.77), discontinuation rate was 18% (91/504) vs. 3% (36/434) (Z = 4.78; p < 0.00001; RR = 2.41), and death rate was 2.6% (13/504) vs. 0.7% (3/434) (Z = 1.90; p = 0.06; RR = 2.77). Conclusions: It was observed that the combined (durvalumab and tremelimumab) vs. monotherapy (durvalumab) is associated with a higher risk of treatment discontinuation, mortality, fever, diarrhea, rash, pruritis, and reduced appetite. This information is relevant and should be disclosed, especially to patients that are currently enrolled in clinical trials considering this combined therapy. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: The Development of Cancer Immunotherapy)

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