[Mechanisms of resistance and escape to CAR-T cells].
Fiche publication
Date publication
octobre 2021
Journal
Bulletin du cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr RUBIO Marie Thérèse
Tous les auteurs :
Grinda T, Brouard J, Tran D, Rubio MT
Lien Pubmed
Résumé
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.
Mots clés
CAR-T cells, Cellules CAR-T, Immunosuppressive microenvironment, Loss of antigen, Lymphocyte depletion, Microenvironnement immunosuppresseur, Perte d’antigène, Tumor escape, Échappement tumoral, Épuisement lymphocytaire
Référence
Bull Cancer. 2021 Oct;108(10S):S128-S140