4.7 Review

Genetic engineering of T cells for immunotherapy

Journal

NATURE REVIEWS GENETICS
Volume 22, Issue 7, Pages 427-447

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41576-021-00329-9

Keywords

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Funding

  1. NIH [U19AI117950, U19AI149680, UM1AI126620, UG3DK122644]
  2. Helmsley Charitable Trust
  3. Tmunity Therapeutics

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Genetically engineered T cell immunotherapies have shown remarkable success in treating B cell acute lymphoblastic leukemia by using a patient's own T cells to target cancer cells. However, more complex levels of genetic regulation will be necessary to ensure safety and efficacy in future therapies.
Genetically engineered T cell immunotherapies have provided remarkable clinical success to treat B cell acute lymphoblastic leukaemia by harnessing a patient's own T cells to kill cancer, and these approaches have the potential to provide therapeutic benefit for numerous other cancers, infectious diseases and autoimmunity. By introduction of either a transgenic T cell receptor or a chimeric antigen receptor, T cells can be programmed to target cancer cells. However, initial studies have made it clear that the field will need to implement more complex levels of genetic regulation of engineered T cells to ensure both safety and efficacy. Here, we review the principles by which our knowledge of genetics and genome engineering will drive the next generation of adoptive T cell therapies. This Review discusses strategies for the genetic engineering of adoptive T cell immunotherapies with a focus on approaches harnessing transgenic T cell receptors or chimeric antigen receptors to treat cancer. The authors also discuss the more complex levels of genetic regulation that will be needed to ensure both safety and efficacy.

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