CAR-T-Cell-Based Cancer Immunotherapies: Potentials, Limitations, and Future Prospects.

Abstract

Cancer encompasses various elements occurring at the cellular and genetic levels, necessitating an immunotherapy capable of efficiently addressing both aspects. T cells can combat cancer cells by specifically recognizing antigens on them. This innate capability of T cells has been used to develop cellular immunotherapies, but most of them can only target antigens through major histocompatibility complexes (MHCs). New gene-editing techniques such as clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-cas9) can precisely edit the DNA sequences. CRISPR-cas9 has made it possible to generate genetically engineered chimeric antigen receptors (CARs) that can overcome the problems associated with old immunotherapies. In chimeric antigen receptor T (CAR-T) cell therapy, the patient's T cells are isolated and genetically modified to exhibit synthetic CAR(s). CAR-T cell treatment has shown remarkably positive clinical outcomes in cancers of various types. Nevertheless, there are various challenges that reduce CAR-T effectiveness in solid tumors. It is required to address these challenges in order to make CAR-T cell therapy a better and safer option. Combining CAR-T treatment with other immunotherapies that target multiple antigens has shown positive outcomes. Moreover, recently generated Boolean logic-gated advanced CARs along with artificial intelligence has expanded its potential to treat solid tumors in addition to blood cancers. This review aims to describe the structure, types, and various methods used to develop CAR-T cells. The clinical applications of CAR-T cells in hematological malignancies and solid tumours have been described in detail. In addition, this discussion has addressed the limitations associated with CAR-T cells, explored potential strategies to mitigate CAR-T-related toxicities, and delved into future perspectives.