AI Article Synopsis
- CAR-T cells are a promising anti-tumor immunotherapy that enhances T cell recognition and targeting of cancer cells, particularly effective against B cell malignancies like lymphomas and leukemias, with high response rates.
- Despite their success, 30-50% of patients experience treatment escape, and the effectiveness of CAR-T therapy for solid tumors is still limited due to various factors.
- Understanding the mechanisms of resistance and optimizing CAR-T cell design, as well as integrating combination therapies, could improve patient responses and manage tumor microenvironments more effectively.
Article Abstract
CAR-T cells represent a new approach to anti-tumor cellular immunotherapy allowing to combine the recognition of tumor antigens on target cells and the activation, proliferation and cytotoxic capacity of T lymphocytes. Impressive clinical results have been obtained with CAR-T cells targeting the CD19 antigen in relapsing or refractory B cell malignant lymphomas or acute lymphoblastic leukemias, with complete response rates of 40 to 90%. However, 30 to 50% of responding patients in B malignancies will escape treatment secondarily, and the effectiveness of these approaches in solid tumors remains limited. Different mechanisms of primary resistance and/or escape to CAR-T cells have been described. This review aims to describe these mechanisms and explore potential ways for optimization. We will see that the initial response and its long-term persistence depends on several parameters: the functional characteristics of the CAR-T cells in vivo, the expression of targeted antigens on tumor cells, the development of a immunosuppressive microenvironment. Or of an immune response directed against the CAR molecule. In solid tumors in particular, the specificity of the antigen target and the "homing" of CAR-T cells in the tumor site are additional elements to consider. A better knowledge of mechanisms of resistance will help to improve the clinical outcomes by either modulating the construction and the production of CAR-T cells and/or to combine them with other immunotherapeutic approaches to better control the tumor microenvironment.
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| http://dx.doi.org/10.1016/j.bulcan.2021.09.002 | DOI Listing |
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