• Eric Tran, Paul F Robbins, Yong-Chen Lu, Todd D Prickett, Jared J Gartner, Li Jia, Anna Pasetto, Zhili Zheng, Satyajit Ray, Eric M Groh, Isaac R Kriley, and Steven A Rosenberg.
• From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
• N. Engl. J. Med. 2016 Dec 8; 375 (23): 2255-2262.

AbstractWe 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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