Abstract
Chimeric antigen receptor T cell (CAR-T cell) therapy has shown impressive success in the treatment of hematological malignancies, but the systemic toxicity and complex manufacturing process of current autologous CAR-T cell therapy hinder its broader applications. Universal CAR-T cells have been developed to simplify the production process through isolation and editing of allogeneic T cells from healthy persons, but the allogeneic CAR-T cells have recently encountered safety concerns, and clinical trials have been halted by the FDA. Thus, there is an urgent need to seek new ways to overcome the barriers of current CAR-T cell therapy. In-vivo CAR-T cells induced by nanocarriers loaded with CAR-genes and gene-editing tools have shown efficiency for regressing leukemia and reducing systemic toxicity in a mouse model. The in-situ programming of autologous T-cells avoids the safety concerns of allogeneic T cells, and the manufacture of nanocarriers can be easily standardized. Therefore, the in-vivo induced CAR-T cells can potentially overcome the abovementioned limitations of current CAR-T cell therapy. Here, we provide a review on CAR structures, gene-editing tools, and gene delivery techniques applied in immunotherapy to help design and develop new in-vivo induced CAR-T cells.
Highlights
Chimeric antigen receptor T cell (CAR-T cell) therapy is a new cell immunotherapy technique that incorporates synthetic receptors into T cells that recognize and kill tumor cells with a cognate targeting ligand [1, 2]
Enormous achievements have been made in chimeric antigen receptor (CAR)-T cell therapy in the last decade, and five CAR-T cell products are available in the clinic
Current CAR-T cell therapy has some barriers that need to be overcome such as cytokine release syndrome (CRS) and immune effector cellassociated neurotoxicity syndrome (ICANS) toxicity and expensive and complex manufacturing procedures
Summary
Chimeric antigen receptor T cell (CAR-T cell) therapy is a new cell immunotherapy technique that incorporates synthetic receptors into T cells that recognize and kill tumor cells with a cognate targeting ligand [1, 2]. The complex manufacturing process of CAR-T cells limits the broader applications of this therapeutic method as a standard clinical treatment [2, 9,10,11]. In-Vivo Induced CAR-T Cell manufacturing process of CAR-T cells, universal allogeneic CAR-T cells from healthy persons have been tested in clinical trials [12,13,14,15]. We need new strategies to overcome the associated toxicity and simplify the manufacturing process of current CAR-T cell therapy. The insitu programming of autologous CAR-T cells can enhance the targeted killing of tumor cells and reduce systemic toxicity such as CRS and neurotoxicity. The nanocarriers can be manufactured in a standardized method [21] In-vivo induced CAR-T cells provide a potential solution to overcome the barriers of current CAR-T cell therapy. Here, we review CAR structure design, gene-editing tools, and gene delivery systems and the future trend of immune cell therapy
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