Abstract
Treatment with T cells genetically engineered to express tumor-reactive T cell receptors (TCRs), known as TCR-gene therapy (TCR-T), is a promising immunotherapeutic approach for patients with cancer. The identification of optimal TCRs to use and tumor antigens to target are key considerations for TCR-T. In this issue of the JCI, Bear and colleagues report on their use of in vitro assays to characterize four HLA-A*03:01- or HLA-A*11:01-restricted TCRs targeting the oncogenic KRAS G12V mutation. The TCRs were derived from healthy donors or patients with pancreatic cancer who had received a vaccine against mutant KRAS. The most promising TCRs warrant testing in patients with KRAS G12V-positive cancers.
MeSH terms
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Cancer Vaccines / immunology
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HLA-A Antigens / genetics
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HLA-A Antigens / immunology
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HLA-A Antigens / metabolism
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Humans
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Mutation
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Mutation, Missense
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Neoplasms / genetics
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Neoplasms / immunology
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Neoplasms / therapy
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / immunology
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Pancreatic Neoplasms / therapy
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Proto-Oncogene Proteins p21(ras)* / genetics
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Proto-Oncogene Proteins p21(ras)* / immunology
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Proto-Oncogene Proteins p21(ras)* / metabolism
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Receptors, Antigen, T-Cell* / genetics
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Receptors, Antigen, T-Cell* / immunology
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Receptors, Antigen, T-Cell* / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Receptors, Antigen, T-Cell
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Proto-Oncogene Proteins p21(ras)
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KRAS protein, human
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Antigens, Neoplasm
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HLA-A Antigens
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Cancer Vaccines