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Ref Type Journal Article
PMID (27959684)
Authors Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, Kriley IR, Rosenberg SA
Title T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer.
Journal Vol Issue Date Pages Journal Short Title
The New England journal of medicine 375 23 2016 Dec 08 2255-2262 N Engl J Med
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
KRAS mutant-specific TIL KRAS mutant-specific TIL 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
KRAS mutant-specific TIL KRAS-mutant specific autologous tumor-infiltrating cells KRAS-mutant specific autologous tumor-infiltrating cells are patient-derived tumor-infiltrating cells that contain cytotoxic T-cells that target KRAS-mutant tumor cells, which upon expansion and infusion potentially induce regression of KRAS-mutant tumors (PMID: 27959684).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References