Cancer immunotherapies utilizing genetically engineered T cells have emerged as powerful personalized therapeutic agents showing dramatic preclinical and clinical results, particularly in hematological malignancies. Ectopically expressed chimeric antigen receptors (CARs) reprogram immune cells to target and eliminate cancer. However, CAR T cell therapy's success depends on the balance between effective anti-tumor activity and minimizing harmful side effects. To improve CAR T cell therapy outcomes and mitigate associated toxicities, scientists from different fields are cooperating in developing next-generation products using the latest molecular cell biology and synthetic biology tools and technologies. The immunotherapy field is rapidly evolving, with new approaches and strategies being reported at a fast pace. This comprehensive literature review aims to provide an up-to-date overview of the latest developments in controlling CAR T cell activity for improved safety, efficacy, and flexibility.

• Keywords
• CAR, Cancer, Cell therapy, Chimeric antigen receptor, Immunotherapy, Regulation, Synthetic, T cell,
• MeSH
• Receptors, Chimeric Antigen * MeSH
• Immunotherapy, Adoptive adverse effects   methods   MeSH
• Immunotherapy MeSH
• Humans MeSH
• Neoplasms * therapy   MeSH
• Receptors, Antigen, T-Cell MeSH
• T-Lymphocytes MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Receptors, Chimeric Antigen * MeSH
• Receptors, Antigen, T-Cell MeSH

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.

• Keywords
• CAR T-cells, CD10, immunotherapy,
• MeSH
• Antigens, CD19 metabolism   MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell * metabolism   therapy   MeSH
• Immunotherapy, Adoptive MeSH
• Leukemia, B-Cell * metabolism   therapy   MeSH
• Humans MeSH
• Neprilysin * therapeutic use   MeSH
• Receptors, Antigen, T-Cell metabolism   MeSH
• T-Lymphocytes MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antigens, CD19 MeSH
• Neprilysin * MeSH
• Receptors, Antigen, T-Cell MeSH