Design and development of CAR-T cells for cancer therapy

Introduction: Today, treatment with CAR-T cells is accepted as an effective treatment for blood malignancies. CAR-T cells are autologous T cells that are engineered by gene transfer techniques to express a chimeric antigen receptor (CAR). Despite the promising results and the approval of six CAR-T cell products; these products have not yet been approved for solid tumors. In addition, the high cost of treatment with CAR-T cells has limited patients' access to these life-saving drugs. Therefore, key considerations in the design and development of CAR-T cells should be defined and methods of reducing the cost of this treatment method should be investigated. Materials and Methods: This study was performed based on an accurate bibliography through research databases such as PubMed, Scopus, Web of Science, and Google Scholar search engine, as well as the websites of pharmaceutical companies. Results: CAR synthetic receptors contain an antigen-recognizing extracellular region that connects to the space-forming, transmembrane and intracellular messenger regions. Each part of the CAR structure affects some functions of CAR, including target recognition, activation and cell lysis. So far, five generations of CAR-T cells have been developed to improve the messaging capacity of these cells. In addition, gene transfer systems such as electroporation, transposon and genome editing systems have been introduced as an alternative to viral vectors to produce safe and affordable CAR-T cells. Also, the development of ready-to-use products, product production in places far from the place of consumption, new pricing platforms and methods, and health insurance system initiatives have been suggested as ways to reduce prices. Conclusion: In this article, an overview of how to develop CAR-T cells, important factors in the design of chimeric receptors, different methods of gene transfer and solutions to reduce the cost of this treatment were discussed. By using these strategies, the potential of CAR-T cells in cancer immunotherapy can be fully utilized.