Journal
MOLECULAR THERAPY
Volume 29, Issue 11, Pages 3153-3162Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2021.10.001
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Funding
- St. Baldrick's/Stand Up 2 Cancer Pediatric Dream Team translational cancer research grant [SU2CAACR-DT1113]
- Stanford University Cancer Immunotherapy Program
- Virginia and D.K. Ludwig Fund for Cancer Research
- Stanford Medical Scientist Training Program [T32GM007365]
- Stanford Interdisciplinary Graduate Fellowship
- Stanford ChEM-H Chemistry/Biology Interface Predoctoral Training Program
- Stanford ChEM-H O'Leary-Thiry Graduate Fellowship
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Gene editing platforms are being explored to enhance the potency of adoptive T cell therapies by knocking out molecules that inhibit immune responses and improving gene expression profiles. These approaches also aim to create off-the-shelf therapies that can prevent immune rejection, thus increasing the effectiveness and ease of use of these treatments.
Adoptive T cell therapies have shown impressive signals of activity, but their clinical impact could be enhanced by technologies to increase T cell potency and diminish the cost and labor involved in manufacturing these products. Gene editing platforms are under study in this arena to (1) enhance immune cell potency by knocking out molecules that inhibit immune responses; (2) deliver genetic payloads into precise genomic locations and thereby enhance safety and/or improve the gene expression profile by leveraging physiologic promoters, enhancers, and repressors; and (3) enable off-the-shelf therapies by preventing alloreactivity and immune rejection. This review discusses gene editing approaches that have been the best studied in the context of human T cells and adoptive T cell therapies, summarizing their current status and near-term potential for translation.
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