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Cancers
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Significance of CAR T-Cell Therapy in Aggressive B-Cell Lymphoma Treatment
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Significance of CAR T-Cell Therapy in Aggressive B-Cell Lymphoma Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 3652

Editor

Dr. Wing Keung Chan

E-Mail Website
Guest Editor
Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH 43210, United States
Interests: chimeric antigen receptor; immunotherapy; antibody engineering; NK cell therapy

Special Issue Information

Dear Colleagues,

Recently FDA-approved, patients who have relapsed non-Hodgkin and Hodgkin lymphomas can be treated with anti-CD19 CAR-T therapy. Extensive basic and translational research provides insights into the efficacy, toxicity, and potential resistance mechanisms of these therapies. While CAR-T therapy offers significant clinical benefits, efforts to enhance its efficacy and reduce its toxicity are ongoing.

This Special Issue aims to publish research articles and reviews on the following topics:

  1. Current updates on the efficacy and immune-related adverse events of the six CAR-T therapies that have been FDA-approved for treating refractory and relapsed lymphomas, such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, high-grade B-cell lymphoma, transformed follicular lymphoma, and primary/secondary central nervous system lymphoma.
  2. Preclinical or clinical trial studies on combination therapies with CAR-T cells.

Novel target discovery and multidimensional omics data analyses of the lymphoma microenvironment and CAR-T persistence in aggressive B-cell lymphoma.

Dr. Wing Keung Chan
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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • CAR-T therapy
  • non-hodgkin lymphoma
  • hodgkin lymphoma
  • CAR-T persistence
  • immune-related adverse events (irAEs)
  • resistance mechanisms
  • combination therapy
  • tumor microenvironment
  • multiomics data analysis

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Published Papers (2 papers)

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Review

15 pages, 419 KB  
Review
The Great Debate: CAR-T-Cell Therapy Versus Bispecific Antibodies in B-Cell Lymphoma
by Massimo Martino, Violetta Marafioti, Martina Pitea, Gaetana Porto, Giorgia Policastro, Filippo Antonio Canale, Virginia Naso and Caterina Alati
Cancers 2026, 18(15), 2513; https://doi.org/10.3390/cancers18152513 - 5 Aug 2026
Viewed by 432
Abstract
Background: The treatment paradigm for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) has undergone significant change with the advent of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies and CD20 × CD3 bispecific antibodies (BsAbs). Although both approaches have shown high response rates in single-arm [...] Read more.
Background: The treatment paradigm for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) has undergone significant change with the advent of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies and CD20 × CD3 bispecific antibodies (BsAbs). Although both approaches have shown high response rates in single-arm studies, the absence of prospective randomized head-to-head comparisons has resulted in true clinical equipoise. Methods: A narrative synthesis was conducted, incorporating pivotal and updated phase 2 and 3 trial data, real-world evidence, and published meta-analyses. Results: In the second-line setting, CAR-T therapy demonstrates superior event-free survival, progression-free survival, and overall survival compared to standard-of-care chemo-transplant regimens. In the third-line setting, a pooled meta-analysis indicates significantly higher complete response rates for CAR-T compared with BsAbs, as well as superior 12-month progression-free survival. BsAbs provide immediate availability, greater accessibility, more favorable neurotoxicity profiles, and are feasible for frail or elderly patients. Real-world data show that BsAb complete response rates are consistently lower than those observed in clinical trials, whereas CAR-T real-world effectiveness closely aligns with pivotal trial outcomes. Emerging phase 3 data on fixed-duration and monotherapy bispecific regimens suggest that a genuine, if less mature, curative fraction may also be achievable among BsAb-treated complete responders. Conclusions: CAR-T therapy remains the standard of care for fit, eligible patients with R/R LBCL in second- and third-line settings with curative intent, providing superior depth and durability of response and a growing potential for long-term cure. BsAbs constitute a critical therapeutic alternative for patients ineligible for CAR-T, those with rapidly progressive disease, frail or elderly individuals, and as bridging strategies. A patient-centered, scenario-specific clinical decision framework is recommended. Full article
(This article belongs to the Special Issue Significance of CAR T-Cell Therapy in Aggressive B-Cell Lymphoma Treatment)
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17 pages, 282 KB  
Review
Current Insights of Post-Infusion CAR T Expansion and Persistence for Large B-Cell Lymphoma
by Grace Wolyncewicz, Rebecca Wayte and Edward Abadir
Cancers 2025, 17(19), 3167; https://doi.org/10.3390/cancers17193167 - 29 Sep 2025
Viewed by 2580
Abstract
CD19 directed chimeric antigen receptor (CAR) T-cell therapy is standard of care for relapsed or refractory large B-cell lymphoma. CAR T-cell persistence and activity are associated with outcomes for patients with relapsed B-acute lymphoblastic leukaemia (B-ALL), but the association between expansion kinetics and [...] Read more.
CD19 directed chimeric antigen receptor (CAR) T-cell therapy is standard of care for relapsed or refractory large B-cell lymphoma. CAR T-cell persistence and activity are associated with outcomes for patients with relapsed B-acute lymphoblastic leukaemia (B-ALL), but the association between expansion kinetics and outcome is less clear in the setting of large B-cell lymphoma. CAR T-cell expansion and persistence have been measured in both clinical trials and real-world settings, but the clinical relevance and applicability of these measurements remain unclear. There is increasing evidence that the in vivo kinetics of CAR T-cells post-infusion do offer important predictive insights into patient outcomes; despite this, limitations remain given the heterogeneity in methodology and timing of measurement. This review will summarise methodologies utilised to measure CD19 directed CAR T-cell expansion and persistence in vivo, in addition to the clinical implications of these measurements as currently described. Full article
(This article belongs to the Special Issue Significance of CAR T-Cell Therapy in Aggressive B-Cell Lymphoma Treatment)
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