Immunotherapy of diffuse large B-cell lymphoma: from monoclonal antibodies to cellular therapies - A narrative review

Sep 22, 2026

Uploaded by Mabel

B-cell lymphomas are diverse blood cancers shaped by immunotherapy. Rituximab plus chemoimmunotherapy (R-CHOP) improves outcomes, yet diffuse large B-cell lymphoma (DLBCL) still faces relapse and early resistance, affecting roughly 30–40% of patients. This narrative review summarizes current DLBCL immunotherapy options, detailing mechanisms, clinical results, and safety. Coverage spans bispecific and trispecific antibodies, antibody-drug conjugates, immune checkpoint inhibitors, and immune effector cell therapies including CAR-T and CAR-NK.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Classification and epidemiology of lymphomas

Subtypes and prognostic relevance in DLBCL

Molecular features (e.g., MYC) and targeted implications

TYPE Review PUBLISHED 28 May 2026 DOI 10.3389/fimmu.2026.1835301 OPEN ACCESS EDITED BY Eva Mara Garrido-Martin, Universidad Auto´noma de Madrid, Spain REVIEWED BY Claudio Scuoppo, Sapience Therapeutics, NY, United States Nemanja Maletin, University of Novi Sad, Serbia *CORRESPONDENCE Giuseppe Sconocchia [giuseppe.sconocchia@cnr.it](giuseppe.sconocchia@cnr.it) RECEIVED 20 March 2026 REVISED 29 April 2026 ACCEPTED 11 May 2026 PUBLISHED 28 May 2026 CITATION Aureli A, Lanzilli G, Boccadamo Pompili SV, Spagnoli GC, Sconocchia G and Caratelli S (2026) Immunotherapy of diffuse large B-cell lymphoma: from monoclonal antibodies to cellular therapies. A narrative review. Front. Immunol. 17:1835301 . doi: 10.3389/fimmu.2026.1835301 COPYRIGHT © 2026 Aureli, Lanzilli, Boccadamo Pompili, Spagnoli, Sconocchia and Caratelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Immunotherapy of diffuse large B-cell lymphoma: from monoclonal antibodies to cellular therapies. A narrative review Anna Aureli 1, Giulia Lanzilli 1, Stefano Vito Boccadamo Pompili 1, Giulio Cesare Spagnoli 1, Giuseppe Sconocchia 1,2* and Sara Caratelli 1 1 Department of Biomedicine, Institute of Translational Pharmacology, National Research Council (CNR), Rome, Italy, 2Saint Camillus, International Medical University (UNICAMILLUS), Rome, Italy B-cell lymphomas (BCLs) are a heterogeneous group of blood cancers whose treatment has been signiﬁcantly transformed by immunotherapy. The use of the anti-CD20 monoclonal antibody rituximab, combined with chemotherapy (RCHOP), has markedly improved patient outcomes. However, some subtypes, particularly Diffuse Large B-Cell Lymphoma (DLBCL), remain challenging to treat due to frequent relapses and/or early resistance to therapy. Standard frontline immunochemotherapy is successful in about 60% of DLBCL cases, whereas 30- 40% experience relapse or refractory disease, thus highlighting the urgent need for more effective therapeutic strategies. More recently, advanced immunotherapies have been investigated, relying on the use of innovative bi-and trispeciﬁc antibodies, antibody-drug conjugates, and immune checkpoint inhibitors . Furthermore, immune effector cell-based therapies, such as CAR-T and CARNK cells, have been developed. Among these, CAR-T cell therapy targeting CD19 achieved high response rates in patients with relapsed or refractory DLBCL, emerging as new pivotal therapeutic option. In this narrative review, we provide an overview of current immunotherapy treatments for DLBCL, including underlying mechanisms, clinical outcomes, and safety proﬁles. KEYWORDS B-cell lymphoma, bispeciﬁc antibody, CAR-NK, CAR-T, checkpoint inhibitors, FcgRs, immunotherapy, monoclonal antibody Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; ADCs, antibody–drug conjugates; ASCT, autologous stem cell transplantation; BCL, B-cell lymphomas; BLCL, B-lymphoblastoid cell line; BsAbs, bispeciﬁc antibodies; CAR, chimeric antigen receptor; CDC, complement-dependent cytotoxicity; CPI, immune checkpoint inhibitors; CR, complete remission; CRS, cytokine release syndrome; DLBCL, diffuse large B-cell lymphoma; EMA, European Medicines Agency; FcgCR, Fc gamma chimeric receptors; FcgR, Fc gamma receptors; FDA, Food and Drug Administration; FL, follicular lymphoma; GvHD, graft-versus-host disease; ICANS, immune effector cell–associated neurotoxicity Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) 1 Introduction Lymphomas are a

FAQs

Why is immunotherapy important for diffuse large B-cell lymphoma (DLBCL)?

Immunotherapy has transformed treatment outcomes, but DLBCL remains challenging because a substantial fraction of patients relapse or develop early resistance to standard chemoimmunotherapy.

How does R-CHOP affect outcomes in DLBCL?

R-CHOP improves patient outcomes in the front-line setting, but approximately 30–40% still experience relapse or refractory disease despite treatment.

What therapeutic approaches are highlighted beyond monoclonal antibodies?

The review covers advanced strategies including bispecific/trispecific antibodies, antibody-drug conjugates, immune checkpoint inhibitors, and immune effector cell therapies such as CAR-T and CAR-NK.

Sep 22, 2026

Uploaded by Mabel