T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer
- PMID: 27959684
- PMCID: PMC5178827
- DOI: 10.1056/NEJMoa1609279
T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer
Abstract
We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from a patient with metastatic colorectal cancer. We observed objective regression of all seven lung metastases after the infusion of approximately 1.11×1011 HLA-C*08:02-restricted tumor-infiltrating lymphocytes that were composed of four different T-cell clonotypes that specifically targeted KRAS G12D. However, one of these lesions had progressed on evaluation 9 months after therapy. The lesion was resected and found to have lost the chromosome 6 haplotype encoding the HLA-C*08:02 class I major histocompatibility complex (MHC) molecule. The loss of expression of this molecule provided a direct mechanism of tumor immune evasion. Thus, the infusion of CD8+ cells targeting mutant KRAS mediated effective antitumor immunotherapy against a cancer that expressed mutant KRAS G12D and HLA-C*08:02.
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Comment in
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Drugging the Undruggable Ras - Immunotherapy to the Rescue?N Engl J Med. 2016 Dec 8;375(23):2286-2289. doi: 10.1056/NEJMe1612215. N Engl J Med. 2016. PMID: 27959676 No abstract available.
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T-Cell Transfer Therapy Targeting Mutant KRAS.N Engl J Med. 2017 Feb 16;376(7):e11. N Engl J Med. 2017. PMID: 28199803 Free PMC article. No abstract available.
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T-Cell Transfer Therapy Targeting Mutant KRAS.N Engl J Med. 2017 Feb 16;376(7):e11. doi: 10.1056/NEJMc1616637. N Engl J Med. 2017. PMID: 28207208 No abstract available.
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T-Cell Transfer Therapy Targeting Mutant KRAS.N Engl J Med. 2017 Feb 16;376(7):e11. doi: 10.1056/NEJMc1616637. N Engl J Med. 2017. PMID: 28207209 Free PMC article. No abstract available.
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