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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.

SUBMITTER: Tran E

PROVIDER: S-EPMC5178827 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer.

Tran Eric E Robbins Paul F PF Lu Yong-Chen YC Prickett Todd D TD Gartner Jared J JJ Jia Li L Pasetto Anna A Zheng Zhili Z Ray Satyajit S Groh Eric M EM Kriley Isaac R IR Rosenberg Steven A SA

The New England journal of medicine 20161201 23

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 1.11×10<sup>11</sup> 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 ...[more]

PMID: 27959684

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