Journal
IMMUNOLOGICAL REVIEWS
Volume 257, Issue 1, Pages 145-164Publisher
WILEY
DOI: 10.1111/imr.12141
Keywords
adoptive T-cell therapy; TCR gene therapy; high affinity; preclinical models; clinical trials
Categories
Funding
- National Institutes of Health National Cancer Institute [P01 CA18029, R01 CA33084, K08 CA169485, R01 CA176841]
- Korean Research Institute of Bioscience and Biotechnology
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Cancer Center [CA015704]
- Doug and Maggie Walker Immunotherapy Fellowship
- J. Orin Edson Immunotherapy Pilot Award
- Irvington Institute Fellowship Program of the Cancer Research Institute
- Jack Paul Estate Fund
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Adoptive T-cell therapy involves the isolation, expansion, and reinfusion of T lymphocytes with a defined specificity and function as a means to eradicate cancer. Our research has focused on specifying the requirements for tumor eradication with antigen-specific T cells and T cells transduced to express a defined T-cell receptor (TCR) in mouse models and then translating these strategies to clinical trials. Our design of T-cell-based therapy for cancer has reflected efforts to identify the obstacles that limit sustained effector T-cell activity in mice and humans, design approaches to enhance T-cell persistence, develop methods to increase TCR affinity/T-cell functional avidity, and pursue strategies to overcome tolerance and immunosuppression. With the advent of genetic engineering, a highly functional population of T cells can now be rapidly generated and tailored for the targeted malignancy. Preclinical studies in faithful and informative mouse models, in concert with knowledge gained from analyses of successes and limitations in clinical trials, are shaping how we continue to develop, refine, and broaden the applicability of this approach for cancer therapy.
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