How to eliminate solid tumors by CAR T-cell therapy

Abdul Salam Ahmed, Asma (2020)

TCRs (T-cell receptors) are expressed by T cells, and profoundly and actively influence lymphocyte activity in modulating the immune response. Manipulating T cell receptor properties and numbers to boost immune responses is a very active area of immunotherapy research. TILs (tumor-infiltrating lymphocytes) are being actively investigated for their anti-cancer properties, as tumor biopsies often contain immune cells conditioned to the tumor microenvironment. These cells can be harvested, studied, and subjected to chemokine fortification prior to reintroduction. So, CAR-T cells (chimeric antigen receptor-T cells) refers to genetically engineered T cells which express surface receptors specifically targeting cancer cell-expressed surface antigen. (1) CARs are engineered fusion proteins that contain an extracellular antigen-binding domain composed of a single chain variable fragment derived from an antibody and intracellular signaling domains, which are involved in the initiation of T-cell signaling and downstream T-cell effector functions .


T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited ,It's because solid tumors don't seem to be the identical . Oncolytic viruses have the potential to act in synergy with immunotherapies because of their immunogenic oncolytic properties and also the opportunity of incorporating therapeutic transgenes in their genomes. hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the end result of CART-cell therapy in solid tumors. demonstrated that OAd-BiTE– mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile. BiTEs secreted from infected cells redirected CART cells toward EGFR within the absence of FR-a, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells.

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