title: 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 1.11×1011HLA-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.
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Eric
authors.initials: E
authors.lastname: Tran
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Yong-Chen
authors.initials: YC
authors.lastname: Lu
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Prickett
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Gartner
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Anna
authors.initials: A
authors.lastname: Pasetto
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Ray
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Groh
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Kriley
authors.affiliation: From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D018414:CD8-Positive T-Lymphocytes; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D018655:Lymphocyte Count; D008875:Middle Aged; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)