T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer
Eric Tran(National Institutes of Health), Paul F. Robbins(National Institutes of Health), Yong‐Chen Lu(National Institutes of Health), Todd D. Prickett(National Institutes of Health), Jared J. Gartner(National Institutes of Health), Lee Jia(National Institutes of Health), Anna Pasetto(National Institutes of Health), Zhili Zheng(National Institutes of Health), Satyajit Ray(National Institutes of Health), Eric Groh(National Institutes of Health), Isaac Kriley(National Institutes of Health), Steven A. Rosenberg(National Institutes of Health)
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Abstract
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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