Abstract
Remarkable progress has been made in the field of cancer immunotherapy in the past few years. Immunotherapy has become a standard treatment option for patients with various cancers, including melanoma, lymphoma, and carcinomas of the lungs, kidneys, bladder, and head and neck. Promising immunotherapy approaches, such as chimeric antigen receptor (CAR) T cell therapy and therapeutic blockade of immune checkpoints, in particular cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 pathway (PD-1/PD-L1), have boosted the development of new therapeutic regimens for patients with cancer. Immunotherapeutic strategies for diffuse large B-cell lymphoma (DLBCL) include monoclonal anti-CD20 antibody (rituximab), monoclonal anti-PD-1 antibodies (nivolumab and pembrolizumab), monoclonal anti-PD-L1 antibodies (avelumab, durvalumab, and atezolizumab) and chimeric antigen receptor (CAR) T cell therapy. In this review, we outline the latest highlights and progress in using immunotherapy to treat patients with DLBCL, with a focus on the therapeutic blockade of PD-1/PD-L1 and CAR T cell therapy in DLBCL. We also discuss current clinical trials of PD-1/PD-L1 and CAR T cell therapy and review the challenges and opportunities of using immunotherapy for the treatment of DLBCL.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma
Another phase II clinical trial of durvalumab in combination with monoclonal antibodies directed against CD20, OX40 and cytotoxic T lymphocyte-associated protein 4 (CTLA4) designed to determine the optimal dose of MEDI6469 that is safe and tolerable in participants with diffuse large B-cell lymphoma (DLBCL) was terminated early at the sponsor’s discretion due technical problems (NCT02205333)
In order to enhance their tumor cell-killing efficacy and impact local suppressive cells, fourth-generation chimeric antigen receptor (CAR) T cells were engineered with an inducible expression component, such as cytokine IL-12, and are known as T cells redirected for universal cytokine-mediated killing (TRUCKs)
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Five phase I/II studies are underway to evaluate the efficacy of durvalumab in combination with antibodies, small molecular inhibitors, and chemotherapy as well as CAR T cell therapy in participants with DLBCL Another phase II clinical trial of durvalumab in combination with monoclonal antibodies directed against CD20, OX40 and CTLA4 designed to determine the optimal dose of MEDI6469 (anti-OX40) that is safe and tolerable in participants with DLBCL was terminated early at the sponsor’s discretion due technical problems (NCT02205333). Another human IgG1 anti-PD-L1 monoclonal antibody is avelumab. An ongoing phase III study is evaluating the efficacy of avelumab in combination with a variety of agents for relapsed or refractory DLBCL patients; these agents include utomilumab (anti-4-1BB/CD137), rituximab, azacitidine,
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