T-cell transfer therapy targeting mutant KRAS in cancer
New England Journal of Medicine, 2016•Mass Medical Soc
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 …
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 …
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.
The New England Journal Of Medicine