Despite significant advancements, relapses, and persistent malignancies are still a major challenge faced by the oncologists. Immunotherapy has shown remarkable potential in induction of sustained remission in refractory malignancies. Chimeric antigen receptor T-cell (CAR-T) therapy is a newer treatment methodology approved by the Food and Drug Administration (FDA). The chimeric pairing of an antigen receptor with the T-cell receptor (TCR) intracellular signaling domain allows cluster of designation 8 (CD8) cytotoxic T-cells to target cell surface makers independent of major histocompatibility complex (MHC) activation. Another essential feature which contributes to the broad applicability of CARs and expanding their potential targets is their ability to bind not only to proteins but also to carbohydrate and glycolipid structures. Their antigen-specific and targeted immune responses have shown promising outcomes in clinical trials particularly involving B-cell malignancies and solid tumors. High remission rates and low percentages of relapses have caused a paradigm shift in the treatment of relapsed or refractory cancers. Challenges include side effects such as cytokine release syndrome, on-target off-tumor toxicities, and replication of its success in treating solid tumors. The burden of side effects and hefty cost of treatment are major obstacles which could hinder its progress globally. Nevertheless, ongoing research would only result in a maximized therapeutic potential in addition to more patient- and cost-friendly treatment. In this review, we aim to provide the readers an overview of chimeric antigen receptor T-cell therapy, a relatively new advancement in the world of immuno-oncology and thereby also discussing its advantages, side effects and future challenges.
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http://dx.doi.org/10.7759/cureus.3486 | DOI Listing |
Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.
View Article and Find Full Text PDFCancer Rep (Hoboken)
January 2025
Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China.
Objective: This study aims to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in treating small-cell lung cancer (SCLC) and determine the role of PD-1 monoclonal antibodies in improving patient outcomes.
Methods: A retrospective analysis was performed on 37 SCLC patients who received PD-1 or PD-L1 inhibitors along with chemotherapy at the First Hospital of Lanzhou University between June 2018 and June 2023. Treatment effectiveness was measured by overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS), utilizing chi-square and T-tests, along with Kaplan-Meier and log-rank analyses.
J Hematol Oncol
January 2025
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.
View Article and Find Full Text PDFJ Transl Med
January 2025
Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230031, Anhui, China.
Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.
Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.
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