Optimization of CAR-T Cell-Based Therapies Using Small-Molecule-Based Safety Switches.

Abstract

Chimeric antigen receptor T cell therapy has demonstrated antileukemia efficacy. However, this therapeutic approach is hampered by severe cytokine release syndrome, which is a major impediment to its widespread application in the clinic. The safety of this approach can be improved by engineering a rapid and reversible "off" or "on" safety switch for CAR-T cells. Cutting-edge investigations combining the advantages of genetic engineering and chemical technology have led to the invention of small-molecule-based safety switches for CAR-T cells. Small molecules such as FITC, folate, rimiducid, rapamycin, proteolysis-targeting chimera (PROTAC) compounds, and dasatinib are being investigated to design such safety switches. Optimized CAR-T cells may have enhanced therapeutic efficiency with fewer adverse effects. Herein we summarize and classify current novel small-molecule-based safety switches for CAR-T cells that aim to provide pharmacological control over the activities and toxicities associated with CAR-T cell-based cancer immunotherapies.

• Authors: Yanjun Zheng, Kutty Selva Nandakumar, Kui Cheng
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 64 Issue 14 Pg. 9577-9591 (07 22 2021) ISSN: 1520-4804 [Electronic] United States
• PMID: 34191515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Small Molecule Libraries

Topics

• Antineoplastic Agents (therapeutic use)
• Humans
• Immunotherapy, Adoptive
• Leukemia (therapy)
• Molecular Structure
• Small Molecule Libraries (therapeutic use)