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N Engl J Med. 2016 Dec 8;375(23):2255-2262.

T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer.

Author information

1
From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.

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.

PMID:
27959684
PMCID:
PMC5178827
DOI:
10.1056/NEJMoa1609279
[Indexed for MEDLINE]
Free PMC Article

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