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.
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
Current Gene Therapy
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.
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Cite this article as:
Wang Wei and Wang Yongsheng, Equipping CAR-Modified T Cells with a Brake to Prevent Chronic Adverse Effects, Current Gene Therapy 2012; 12 (6) . https://dx.doi.org/10.2174/156652312803519751
DOI https://dx.doi.org/10.2174/156652312803519751 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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