Making Potent CAR T Cells Using Genetic Engineering and Synergistic Agents

Abstract

Immunotherapies are emerging as powerful weapons for the treatment of malignancies. Chimeric antigen receptor (CAR)-engineered T cells have shown dramatic clinical results in patients with hematological malignancies. However, it is still challenging for CAR T cell therapy to be successful in several types of blood cancer and most solid tumors. Many attempts have been made to enhance the efficacy of CAR T cell therapy by modifying the CAR construct using combination agents, such as compounds, antibodies, or radiation. At present, technology to improve CAR T cell therapy is rapidly developing. In this review, we particularly emphasize the most recent studies utilizing genetic engineering and synergistic agents to improve CAR T cell therapy.

Lenalidomide improves NKG2D-based CAR-T cell activity against colorectal cancer cells invitro

“…Genetically modified T cells, also known as CAR T cells, can bind to tumor-specific antigens by expressing artificial receptors on their cell surfaces. Throughout the past decade, CAR T cells have played a crucial role in the fight against cancer and have made some considerable advances [ 23 , 24 ].…”

Current and Future Perspectives for Chimeric Antigen Receptor T Cells Development in Poland

“…Indeed, 4-1BB-expressing CAR-T cells differentiate into CD45RO(+)CCR7(+) central memory cells and express high amounts of memory-associated transcription factors (incl. KLF6 and JUN), while CD28-expressing CAR-T cells differentiate into short-lived CD45RO(+)CCR7(-) effector cells [ 41 , 42 ]. Furthermore, 4-1BB-CAR-T cells show less exhausted phenotype following ex vivo expansion and express less inhibitory molecules, such as PD-1, CTLA-4 and LAG-3, compared to CD28-CAR-T cells [ 43 , 44 ].…”

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility

“…Many excellent reviews have been published on emerging CAR T cell technologies. The reviews cover a large variety of topics, including CAR switches and modular approaches [17][18][19][20][21][22][23][24][25], approaches to side effect management [14,15,26,27], innovative design of the CARs [28][29][30][31][32][33][34], CAR T cell modifications for targeting to solid tumors [25,35,36], or general reviews about the broad topic [14,15,[37][38][39][40][41][42][43]. However, a comprehensive description of experimentally tested approaches to control CAR T cell functions might provide a valuable reference to researchers and clinicians.…”