title: Re-adapting T cells for cancer therapy: from mouse models to clinical trials.
abstract: 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.
authors: Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Immunology, University of Washington, Seattle, WA, USA.
authors: Ingunn M
authors: IM
authors: Stromnes
authors: Thomas M
authors: TM
authors: Schmitt
authors: Aude G
authors: AG
authors: Chapuis
authors: Sunil R
authors: SR
authors: Hingorani
authors: Philip D
authors: PD
authors: Greenberg
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018929:Cell Culture Techniques; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005818:Genetic Engineering; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D057170:Translational Research, Biomedical; D019139:Tumor Escape / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell
keywords: TCR gene therapy; adoptive T-cell therapy; clinical trials; high affinity; preclinical models