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T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer.

N Engl J Med.. 2016-12;  375:2255-2262
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. Surgery Branch, National Cancer Institute, 10 Center Dr., MSC 1201, Bethesda, MD 20892.
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摘要

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 1.11Χ1011 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 direc... More

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