Title:Equipping CAR-Modified T Cells with a Brake to Prevent Chronic Adverse Effects
Volume: 12
Issue: 6
Author(s): Wei Wang and Yongsheng Wang
Affiliation:
Keywords:
Chimeric antigen receptor, CD19, T lymphocytes, safety, tumor, Chimeric antigen receptor, CD19, T lymphocytes, safety, tumor, cytokines release, proliferative capacity, in vivo survival time
Abstract: Genetical modification of T lymphocytes by chimeric antigen receptor (CAR), which has the affinity to tumor
associated antigen (TAA), can redirect the normal T lymphocytes with tumor specificity. Through optimization of the
CAR construct from first generation to third generation, the properties of these CAR-modified T lymphocytes, including,
cytokines release, proliferative capacity, in vivo survival time, have been remarkably improved. These improvements accelerate
the clinical applications of the CAR-modified T lymphocytes. Due to CD19, and CD20 specificity, CARmodified
T lymphocytes have been clinically used to treat leukemia. Notably, T lymphocytes genetically engineered by
Carl June group with CAR targeting to CD19 have expanded more than 1,000 folds by clearing all CD19 positive leukemia
cells, even the normal B cells, which infiltrated in bone marrow, and survived for more than 6 months. This encouraging
report demonstrates the overwhelming tumor-lytic ability of the CAR-modified T lymphocytes; it also raises the concern
about the chronic toxicity. Here, we emphasize the safety concern when using the CAR-modified T lymphocytes. We
also summarize strategies exploited to clear the genetically engineered T lymphocytes under an urgent condition, which
increases the safety and optimizes the applications of the CAR-modified T lymphocytes.
