title: New Strategies in Engineering T-cell Receptor Gene-Modified T cells to More Effectively Target Malignancies.
abstract: The immune system, T cells in particular, have the ability to target and destroy malignant cells. However, antitumor immune responses induced from the endogenous T-cell repertoire are often insufficient for the eradication of established tumors, as illustrated by the failure of cancer vaccination strategies or checkpoint blockade for most tumors. Genetic modification of T cells to express a defined T-cell receptor (TCR) can provide the means to rapidly generate large numbers of tumor-reactive T cells capable of targeting tumor cells in vivo. However, cell-intrinsic factors as well as immunosuppressive factors in the tumor microenvironment can limit the function of such gene-modified T cells. New strategies currently being developed are refining and enhancing this approach, resulting in cellular therapies that more effectively target tumors and that are less susceptible to tumor immune evasion.
authors.affiliation: Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schmitt
authors.affiliation: Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Immunology, University of Washington, Seattle, Washington.
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stromnes
authors.affiliation: Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Aude G
authors.initials: AG
authors.lastname: Chapuis
authors.affiliation: Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Immunology, University of Washington, Seattle, Washington. Department of Medicine, Division of Medical Oncology, University of Washington School of Medicine, Seattle, Washington. pgreenberg@fhcrc.org.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins