Emerging Novel Combined CAR-T Cell Therapies

Simple Summary As a result of FDA approval of CAR-T cell treatments in the last few years, this immunotherapy has provided further direction to precision medicine through its combination with other therapeutic approaches. In the past year, several review articles have been published focusing on advances in this fast-developing field, especially with respect to efforts to overcome hurdles associated with applying CAR-T cells in solid tumors. This review paper focuses on combining CAR-T cell therapy with small molecule drugs, up-to-date progress in CAR-T cell therapy research, and advances in combined CAR-T immunotherapy with other treatments targeting solid tumors. Chimeric antigen receptors (CAR) T cells are T cells engineered to express membrane receptors with high specificity to recognize specific target antigens presented by cancer cells and are co-stimulated with intracellular signals to increase the T cell response. CAR-T cell therapy is emerging as a novel therapeutic approach to improve T cell specificity that will lead to advances in precision medicine. CAR-T cells have had impressive outcomes in hematological malignancies. However, there continue to be significant limitations of these therapeutic responses in targeting solid malignancies such as heterogeneous antigens in solid tumors, tumor immunosuppressive microenvironment, risk of on-target/off-tumor, infiltrating CAR-T cells, immunosuppressive checkpoint molecules, and cytokines. This review paper summarizes recent approaches and innovations through combination therapies of CAR-T cells and other immunotherapy or small molecule drugs to counter the above disadvantages to potentiate the activity of CAR-T cells.