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Tytuł pozycji:

Rational discovery of a cancer neoepitope harboring the KRAS G12D driver mutation.

Tytuł:
Rational discovery of a cancer neoepitope harboring the KRAS G12D driver mutation.
Autorzy:
Bai P; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
Zhou Q; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
Wei P; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.; Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.
Bai H; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
Chan SK; Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.; Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO, 80045, USA.; Division of Pediatric Allergy-Immunology, National Jewish Health, Denver, CO, 80206, USA.
Kappler JW; Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.; Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, USA.; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.; Structural Biology and Biochemistry program, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Marrack P; Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Yin L; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China. .
Źródło:
Science China. Life sciences [Sci China Life Sci] 2021 Dec; Vol. 64 (12), pp. 2144-2152. Date of Electronic Publication: 2021 Mar 16.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Beijing : Science China Press, co-published with Springer
MeSH Terms:
Mutation*
Antigens, Neoplasm/*genetics
HLA-C Antigens/*genetics
Neoplasms/*genetics
Proto-Oncogene Proteins p21(ras)/*genetics
Antigens, Neoplasm/immunology ; Epitopes ; HLA-C Antigens/metabolism ; HLA-C Antigens/ultrastructure ; Humans ; Immunotherapy ; Major Histocompatibility Complex ; Neoplasms/immunology ; Phylogeny ; Protein Structure, Tertiary ; Proto-Oncogene Proteins p21(ras)/metabolism ; Proto-Oncogene Proteins p21(ras)/ultrastructure
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Contributed Indexing:
Keywords: antigen immunogenicity; cancer immunology; major histocompatibility complex (MHC); neoantigen prediction; vaccine
Substance Nomenclature:
0 (Antigens, Neoplasm)
0 (Epitopes)
0 (HLA-C Antigens)
0 (KRAS protein, human)
EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
Entry Date(s):
Date Created: 20210319 Date Completed: 20220318 Latest Revision: 20220318
Update Code:
20240105
DOI:
10.1007/s11427-020-1888-1
PMID:
33740187
Czasopismo naukowe
Cytotoxic T cells targeting cancer neoantigens harboring driver mutations can lead to durable tumor regression in an HLAI-dependent manner. However, it is difficult to extend the population of patients who are eligible for neoantigen-based immunotherapy, as immunogenic neoantigen-HLA pairs are rarely shared across different patients. Thus, a way to find other human leukocyte antigen (HLA) alleles that can also present a clinically effective neoantigen is needed. Recently, neoantigen-based immunotherapy targeting the KRAS G12D mutation in patients with HLA-C*08:02 has shown effectiveness. In a proof-of-concept study, we proposed a combinatorial strategy (the combination of phylogenetic and structural analyses) to find potential HLA alleles that could also present KRAS G12D neoantigen. Compared to in silico binding prediction, this strategy avoids the uneven accuracy across different HLA alleles. Our findings extend the population of patients who are potentially eligible for immunotherapy targeting the KRAS G12D mutation. Additionally, we provide an alternative way to predict neoantigen-HLA pairs, which maximizes the clinical usage of shared neoantigens.
(© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

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