Copyright © 2016 Massachusetts Medical Society. All rights reserved. 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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Tran, E., Robbins, P. F., Lu, Y.-C., Prickett, T. D., Gartner, J. J., Jia, L., … Rosenberg, S. A. (2016). T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. New England Journal of Medicine, 375(23), 2255–2262. https://doi.org/10.1056/nejmoa1609279
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