PMID- 36705409 OWN - NLM STAT- MEDLINE DCOM- 20230201 LR - 20230215 IS - 2050-4527 (Electronic) IS - 2050-4527 (Linking) VI - 11 IP - 1 DP - 2023 Jan TI - Epitope identification for p53R273C mutant. PG - e752 LID - 10.1002/iid3.752 [doi] LID - e752 AB - BACKGROUND: With the rise of immunotherapy based on cancer neoantigen, identification of neoepitopes has become an urgent problem to be solved. The TP53 R273C mutation is one of the hotspot mutations of TP53, however, the immunogenicity of this mutation is not yet clear. The aim of this study is to identify potential epitopes for p53R273C mutant. METHODS: In this study, bioinformatic methods, peptide exchange assay, and peptide-immunized human leukocyte antigen (HLA) transgenic mouse model were used to explore the immunogenicity of this mutation. RESULTS: Peptides with higher affinity to common HLA-A alleles (A*11:01, A*02:01) were discovered by computational prediction. All the 8-11 mer peptides contain the mutation site were synthesized and soluble peptides were used in the peptide exchange assay. However, the exchange efficiencies of these predicted peptides to HLAs were lower. Fortunately, other peptides with higher exchange efficiency were discovered. Then, the immunogenicity of these peptides was validated with the HLA-A2 transgenic mice model. CONCLUSION: We identified three potential neoepitopes of p53(R273C) for HLA-A*02:01, one potential neoepitope for HLA-A*11:01 and no neoepitope for HLA-A*24:02. CI - (c) 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. FAU - Zhang, Jian AU - Zhang J AUID- ORCID: 0000-0001-8516-8651 AD - School of Medicine, Nankai University, Tianjin, China. AD - Department of Oncology, Oncology Laboratory, Chinese PLA General Hospital, Beijing, China. AD - Research and Development Department, Beijing DCTY Biotech Co., Ltd., Beijing, People's Republic of China. FAU - Liu, Minglu AU - Liu M AD - Department of Oncology, Oncology Laboratory, Chinese PLA General Hospital, Beijing, China. FAU - Chen, Yin AU - Chen Y AD - Research and Development Department, Beijing DCTY Biotech Co., Ltd., Beijing, People's Republic of China. FAU - Zhou, Zishan AU - Zhou Z AD - Research and Development Department, Beijing DCTY Biotech Co., Ltd., Beijing, People's Republic of China. FAU - Wang, Ping AU - Wang P AD - Research and Development Department, Beijing DCTY Biotech Co., Ltd., Beijing, People's Republic of China. FAU - Yu, Yang AU - Yu Y AD - Research and Development Department, Beijing DCTY Biotech Co., Ltd., Beijing, People's Republic of China. FAU - Jiao, Shunchang AU - Jiao S AD - School of Medicine, Nankai University, Tianjin, China. AD - Department of Oncology, Oncology Laboratory, Chinese PLA General Hospital, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immun Inflamm Dis JT - Immunity, inflammation and disease JID - 101635460 RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes) RN - 0 (HLA Antigens) RN - 0 (Peptides) RN - 0 (Tumor Suppressor Protein p53) SB - IM MH - Animals MH - Humans MH - Mice MH - *Antigens, Neoplasm/genetics MH - Epitopes MH - HLA Antigens/genetics MH - Mice, Transgenic MH - *Neoplasms MH - Peptides/genetics MH - *Tumor Suppressor Protein p53/genetics PMC - PMC9761341 OTO - NOTNLM OT - TP53 R273C mutation OT - immunogenicity OT - immunotherapy OT - neoantigen COIS- Authors Yin Chen, Zishan Zhou Ping Wang, and Yu Yang are employed by Beijing DCTY Biotech Co., Ltd., Beijing, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/01/28 06:00 MHDA- 2023/01/31 06:00 PMCR- 2022/12/19 CRDT- 2023/01/27 08:22 PHST- 2022/11/08 00:00 [revised] PHST- 2022/09/06 00:00 [received] PHST- 2022/12/02 00:00 [accepted] PHST- 2023/01/27 08:22 [entrez] PHST- 2023/01/28 06:00 [pubmed] PHST- 2023/01/31 06:00 [medline] PHST- 2022/12/19 00:00 [pmc-release] AID - IID3752 [pii] AID - 10.1002/iid3.752 [doi] PST - ppublish SO - Immun Inflamm Dis. 2023 Jan;11(1):e752. doi: 10.1002/iid3.752.