Advancing Chimeric Antigen Receptor-Engineered T-Cell Immunotherapy Using Genome Editing Technologies: Challenges and Future Prospects

Chimeric antigen receptor engineered-T (CAR-T) cells also named as living drugs, have been recently known as a breakthrough technology and were applied as an adoptive immunotherapy against different types of cancer. They also attracted widespread interest because of the success of B-cell malignancy therapy achieved by anti-CD19 CAR-T cells. Current genetic toolbox enabled the synthesis of CARs receptors which are targeted against tumor-specific antigens, and enabled to arbitrarily T-cells function reprogramming. Approximately all of CAR-T cell based studies apply autologous CAR-T cells in which, modified T-cells are engineered using patient’s own T cells. Currently, four different generation of CAR-T cells have been developed, and the evolution of this kind of therapy illustrates an excellent example of the application of basic research into the clinical trial stage. However, development of allogenic CAR-T cells can be a turning point for CAR-T cells therapy. Appearance of the reliable gene editing approach, CRISPR/Cas9 system, provided a new hope for designing universal CAR-T cells which are off-the-shelf, and enable to use for treatment of any patient with any kind of tumor. This review outlined four different generations of CAR-T cells. Also, we discussed different types of genome editing systems especially CRISPR/Cas9 system, and their capabilities for generating engineered T-cells. Additionally, we tried to explain challenges faced in improving universally generated T-cells.