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Antibody Therapy for Hematologic Malignancies
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Antibody Therapy for Hematologic Malignancies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 4145

Special Issue Editor

Dr. Jonathan P. Butchar

E-Mail Website
Guest Editor
The Ohio State University College of Medicine, Columbus, OH, USA
Interests: leukemia; lymphocytic; chronic; B-cell; tularemia; neoplasms; infection

Special Issue Information

Dear Colleagues,

We are excited to create this Special Issue dedicated to Antibody Therapy for Hematologic Malignancies, which welcomes both original research and review articles. Since the approval of rituximab for CLL in 1997, therapeutic antibodies have taken a major role in the treatment of this disease and others. Although highly effective therapies such as Bruton tyrosine kinase inhibitors, e.g., ibrutinib and acalabrutinib, are now in common use for diseases such as CLL, efforts to improve the impact of antibody therapy—as single-agent or as part of combination therapy—are ongoing. Antibody therapy is becoming more sophisticated, with the design and engineering of bi- and tri-specific forms, and even with cell-based antibody production strategies. In this Special Issue, we wish to include manuscripts that focus on the usage, mechanisms and future potential of antibody therapy for hematologic malignancies. Collectively, we can showcase this established yet still-developing field that continues to impact treatment.

Dr. Jonathan P. Butchar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hematologic malignancies
  • leukemia
  • lymphoma
  • antibody therapy
  • immune therapy
  • cellular therapy
  • combination therapy
  • bispecific
  • BiTE
  • trispecific
  • tumor antigens
  • Fc receptors
  • signaling
  • microenvironment

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Published Papers (3 papers)

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Research

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19 pages, 2376 KiB  
Article
Delineating MYC-Mediated Escape Mechanisms from Conventional and T Cell-Redirecting Therapeutic Antibodies
by Anna Vera de Jonge, Tamás Csikós, Merve Eken, Elianne P. Bulthuis, Pino J. Poddighe, Margaretha G. M. Roemer, Martine E. D. Chamuleau and Tuna Mutis
Int. J. Mol. Sci. 2024, 25(22), 12094; https://doi.org/10.3390/ijms252212094 - 11 Nov 2024
Viewed by 484
Abstract
In B-cell malignancies, the overexpression of MYC is associated with poor prognosis, but its mechanism underlying resistance to immunochemotherapy remains less clear. In further investigations of this issue, we show here that the pharmacological inhibition of MYC in various lymphoma and multiple myeloma [...] Read more.
In B-cell malignancies, the overexpression of MYC is associated with poor prognosis, but its mechanism underlying resistance to immunochemotherapy remains less clear. In further investigations of this issue, we show here that the pharmacological inhibition of MYC in various lymphoma and multiple myeloma cell lines, as well as patient-derived primary tumor cells, enhances their susceptibility to NK cell-mediated cytotoxicity induced by conventional antibodies targeting CD20 (rituximab) and CD38 (daratumumab), as well as T cell-mediated cytotoxicity induced by the CD19-targeting bispecific T-cell engager blinatumomab. This was associated with upregulation of the target antigen only for rituximab, suggesting additional escape mechanisms. To investigate these mechanisms, we targeted the MYC gene in OCI-LY18 cells using CRISPR-Cas9 gene-editing technology. CRISPR-Cas9-mediated MYC targeting not only upregulated CD20 but also triggered broader apoptotic pathways, upregulating pro-apoptotic PUMA and downregulating anti-apoptotic proteins BCL-2, XIAP, survivin and MCL-1, thereby rendering tumor cells more prone to apoptosis, a key tumor-lysis mechanism employed by T-cells and NK-cells. Moreover, MYC downregulation boosted T-cell activation and cytokine release in response to blinatumomab, revealing a MYC-mediated T-cell suppression mechanism. In conclusion, MYC overexpressing tumor cells mitigated the efficacy of therapeutic antibodies through several non-overlapping mechanisms. Given the challenges associated with direct MYC inhibition due to toxicity, successful modulation of MYC-mediated immune evasion mechanisms may improve the outcome of immunotherapeutic approaches in B-cell malignancies. Full article
(This article belongs to the Special Issue Antibody Therapy for Hematologic Malignancies)
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Review

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21 pages, 3444 KiB  
Review
Safety and Efficacy of Bispecific Antibodies in Adults with Large B-Cell Lymphomas: A Systematic Review of Clinical Trial Data
by Elena Bayly-McCredie, Maxine Treisman and Salvatore Fiorenza
Int. J. Mol. Sci. 2024, 25(17), 9736; https://doi.org/10.3390/ijms25179736 - 9 Sep 2024
Viewed by 1754
Abstract
Bispecific antibodies (bsAbs) are an emerging therapy in the treatment of large B-cell lymphomas (LBCLs). There is a gap in the research on the safety and efficacy of bsAbs in adults with LBCL, with current research focusing on the wider non-Hodgkin’s lymphoma population. [...] Read more.
Bispecific antibodies (bsAbs) are an emerging therapy in the treatment of large B-cell lymphomas (LBCLs). There is a gap in the research on the safety and efficacy of bsAbs in adults with LBCL, with current research focusing on the wider non-Hodgkin’s lymphoma population. To address this research gap, we conducted a systematic review aiming to evaluate the safety and efficacy outcomes of bsAbs in adults with LBCL. A systematized search was conducted in PubMed, EMBASE, and CENTRAL on 10 April 2024. Interventional clinical trials were eligible for inclusion. Observational studies, reviews, and meta-analyses were excluded. According to the Revised Risk of Bias Assessment Tool for Nonrandomized Studies, the included studies were largely of a high quality for safety outcome reporting, but of mixed quality for efficacy outcome reporting. Due to the heterogeneity of the included studies, the results were discussed as a narrative synthesis. Nineteen early phase studies were evaluated in the final analysis, with a pooled sample size of 1332 patients. Nine bsAbs were investigated across the studies as monotherapy (nine studies) or in combination regimes (10 studies). The rates of cytokine release syndrome were variable, with any grade events ranging from 0 to 72.2%. Infection rates were consistently high across the reporting studies (38–60%). Cytopenias were found to be common, in particular, anemia (4.4–62%), thrombocytopenia (3.3–69%), and neutropenia (4.4–70%). Immune effector cell-associated neurotoxicity syndrome (ICANS) and grade ≥3 adverse events were not commonly reported. Promising efficacy outcomes were reported, with median overall response rates of 95–100% in the front-line and 36–91% in terms of relapsed/refractory disease. The results of this systematic review demonstrate that bsAbs are generally well-tolerated and effective in adults with LBCL. BsAbs appear to have superior tolerability, but inferior efficacy to CAR T-cell therapies in adults with LBCL. Future research on safety and efficacy should focus on evaluating adverse event timing and management, the impact on the patient’s quality of life, the burden on the healthcare system, and overall survival outcomes. Full article
(This article belongs to the Special Issue Antibody Therapy for Hematologic Malignancies)
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9 pages, 779 KiB  
Review
Loncastuximab Tesirine in the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
by Luis Miguel Juárez-Salcedo, Santosh Nimkar, Ana María Corazón and Samir Dalia
Int. J. Mol. Sci. 2024, 25(14), 7580; https://doi.org/10.3390/ijms25147580 - 10 Jul 2024
Viewed by 1298
Abstract
Currently, a significant percentage of patients with DLBCL are refractory or relapse after a first line of immunochemotherapy. Second relapses after autologous stem cell transplantation or chimeric antigen receptor T-cell therapies present few treatment options and do not yield good results. New molecules [...] Read more.
Currently, a significant percentage of patients with DLBCL are refractory or relapse after a first line of immunochemotherapy. Second relapses after autologous stem cell transplantation or chimeric antigen receptor T-cell therapies present few treatment options and do not yield good results. New molecules have entered the immunotherapy arsenal. Loncastuximab tesirine comprises a humanized anti-CD19 monoclonal conjugated antibody, which consists of an anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Several studies have proven its efficacy in the treatment of refractory cases of DLBCL with a good safety profile, with the main adverse effects being neutropenia, thrombopenia, and liver enzyme involvement. In this review, we explain the mechanism of action of this molecule, the clinical data that have led to its acceptance by the FDA, and the new therapeutic options that are proposed in association with this drug. Full article
(This article belongs to the Special Issue Antibody Therapy for Hematologic Malignancies)
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