Hurdles to breakthrough in CAR T cell therapy of solid tumors

Author:

Marofi Faroogh,Achmad Harun,Bokov Dmitry,Abdelbasset Walid Kamal,Alsadoon Zeid,Chupradit Supat,Suksatan Wanich,Shariatzadeh Siavash,Hasanpoor Zahra,Yazdanifar Mahboubeh,Shomali Navid,Khiavi Farhad Motavalli

Abstract

AbstractAutologous T cells genetically engineered to express chimeric antigen receptor (CAR) have shown promising outcomes and emerged as a new curative option for hematological malignancy, especially malignant neoplasm of B cells. Notably, when T cells are transduced with CAR constructs, composed of the antigen recognition domain of monoclonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner. Despite its beneficial effect, the current CAR T cell therapy approach faces myriad challenges in solid tumors, including immunosuppressive tumor microenvironment (TME), tumor antigen heterogeneity, stromal impediment, and tumor accessibility, as well as tribulations such as on-target/off-tumor toxicity and cytokine release syndrome (CRS). Herein, we highlight the complications that hamper the effectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Medicine,Medicine (miscellaneous)

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