PMID- 33740187
OWN - NLM
STAT- MEDLINE
DCOM- 20220318
LR  - 20220318
IS  - 1869-1889 (Electronic)
IS  - 1674-7305 (Linking)
VI  - 64
IP  - 12
DP  - 2021 Dec
TI  - Rational discovery of a cancer neoepitope harboring the KRAS G12D driver 
      mutation.
PG  - 2144-2152
LID - 10.1007/s11427-020-1888-1 [doi]
AB  - 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.
CI  - (c) 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer 
      Nature.
FAU - Bai, Peng
AU  - Bai P
AD  - State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, 
      College of Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Zhou, Qiuping
AU  - Zhou Q
AD  - State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, 
      College of Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Wei, Pengcheng
AU  - Wei P
AD  - State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, 
      College of Life Sciences, Wuhan University, Wuhan, 430072, China.
AD  - Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, 
      USA.
FAU - Bai, Hua
AU  - Bai H
AD  - State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, 
      College of Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Chan, Sanny K
AU  - Chan SK
AD  - Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, 
      USA.
AD  - Department of Pediatrics, University of Colorado Denver School of Medicine, 
      Aurora, CO, 80045, USA.
AD  - Division of Pediatric Allergy-Immunology, National Jewish Health, Denver, CO, 
      80206, USA.
FAU - Kappler, John W
AU  - Kappler JW
AD  - Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, 
      USA.
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 
      80045, USA.
AD  - Department of Immunology and Microbiology, University of Colorado School of 
      Medicine, Aurora, CO, 80045, USA.
AD  - Structural Biology and Biochemistry program, University of Colorado Anschutz 
      Medical Campus, Aurora, CO, 80045, USA.
FAU - Marrack, Philippa
AU  - Marrack P
AD  - Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, 
      USA.
AD  - Department of Immunology and Microbiology, University of Colorado School of 
      Medicine, Aurora, CO, 80045, USA.
AD  - Department of Biochemistry and Molecular Genetics, University of Colorado 
      Anschutz Medical Campus, Aurora, CO, 80045, USA.
FAU - Yin, Lei
AU  - Yin L
AD  - State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, 
      College of Life Sciences, Wuhan University, Wuhan, 430072, China. 
      yinlei@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210316
PL  - China
TA  - Sci China Life Sci
JT  - Science China. Life sciences
JID - 101529880
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes)
RN  - 0 (HLA-C Antigens)
RN  - 0 (KRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Antigens, Neoplasm/*genetics/immunology
MH  - Epitopes
MH  - HLA-C Antigens/*genetics/metabolism/ultrastructure
MH  - Humans
MH  - Immunotherapy
MH  - Major Histocompatibility Complex
MH  - *Mutation
MH  - Neoplasms/*genetics/immunology
MH  - Phylogeny
MH  - Protein Structure, Tertiary
MH  - Proto-Oncogene Proteins p21(ras)/*genetics/metabolism/ultrastructure
OTO - NOTNLM
OT  - antigen immunogenicity
OT  - cancer immunology
OT  - major histocompatibility complex (MHC)
OT  - neoantigen prediction
OT  - vaccine
EDAT- 2021/03/20 06:00
MHDA- 2022/03/19 06:00
CRDT- 2021/03/19 17:31
PHST- 2020/11/03 00:00 [received]
PHST- 2021/01/14 00:00 [accepted]
PHST- 2021/03/20 06:00 [pubmed]
PHST- 2022/03/19 06:00 [medline]
PHST- 2021/03/19 17:31 [entrez]
AID - 10.1007/s11427-020-1888-1 [pii]
AID - 10.1007/s11427-020-1888-1 [doi]
PST - ppublish
SO  - Sci China Life Sci. 2021 Dec;64(12):2144-2152. doi: 10.1007/s11427-020-1888-1. 
      Epub 2021 Mar 16.