Combination of Pre-existing and New Strategies to Improve CAR-T Cells’ Efficiency

The recent success of CAR-T cell therapy has revolutionized the treatment of cancer.However, its application is currently limited to blood cancers like B-cell leukemia or lymphoma.Major challenges are yet to be resolved before extending it to treat solid tumors, like on-target off-tumor effects, tumor infiltration, immunosuppressive micro-environment, etc. CAR-T cells are down-regulated by mechanisms similar to those suppressing autologous T-cell function.Through genetic deletions, we can eliminate these factors.An interesting factor affecting the CAR-T cells is the lactate-mediated GPR81 receptor.Lactate has been found to play an important role in tumor survival.It carries out functions like metastasis, angiogenesis, and tumor resistance.In addition to current modifications to T-cells required for the therapy, including other cells like dendritic cells for their crucial role in presenting antigens to T-cells and T-cell maturation can aid in tackling problems like lack of identification of tumor antigens.Our technique heavily relies on multiple genetic deletions made possible by CRISPR-Cas9-mediated multiplexing.It is necessary to be able to control the effect of CAR-T cells externally via ON and OFF switches.New advancements have made dose-dependent regulation of CAR-T cells possible instead of complete initiation or termination of their effect.