Abstract 628: Neoantigens predicted by clonal mutation analysis in lung adenocarcinoma patients

Abstract

Abstract Mutant peptides presented in cancer are superior vaccine candidates than self peptides. The efficacy of mutant K-Ras, P53 and EFGR peptides have been tested as cancer vaccines in pancreatic cancer, colorectal cancer, and lung adenocarcinoma. However, the occurrence of these mutations in cancer is limited. Further more, these mutant peptides can only be presented by certain MHC alleles. Neoantigens expressed by passenger mutations which are not involved in common proliferative molecular pathways are potential candidates for personalized vaccine design. Such passenger mutations have drawn attention by the recent clinical data that colorectal cancer with a large number of somatic mutations due to mismatch-repair defects are more susceptible to immune checkpoint blockade by PD1 antibody therapy. In this study, we analyzed the next generation sequencing data of 147 lung adenocarcinoma patients from The Cancer Genome Atlas and predicted neoantigens presented by MHC Class I and Class II molecules. We found 18175 expressed clonal somatic mutations, with an average of 124 per patient. Based on such somatic mutations, we predicted 8731 neo-peptides, among which 3888 strong-binders and 4843 weak-binders to MHC Class I molecules were found by NetMHCPan. For HLA-A*02:01, 778 strong binding and 822 weak binding neo-peptides were found. In average, 11 neo-antigen peptides of mutations were predicted per individual patient with HLA-A*02:01 allele. Smokers expressed 5.73 fold higher mutant neo-antigen peptides than non-smokers. The 20 most commonly mutated genes with predicted neo-antigens are TTN, RYR2, MUC16, KRAS, ZFHX4, TP53, USH2A, NAV3, KEAP1, ANK2, DNAH9, ADAMTS12, CSMD1, CSMD3, SPTA1, FAT3, ZNF804A, PAPPA2, PCLO, EGFR. As a positive control, the frequency of known proliferation-related mutations (KRAS, P53, and EGFR) were determined in 147 patients, which are consistent with previously next generation sequencing studies of lung adenocarcinoma. Mutation hotspots were found in proliferation-related mutations (KRAS), but not in passenger mutations. 6950 neo-peptides, including 259 strong binders and 6691 weak binders were found for HLA DRB1, an MHC Class II molecule. INDEL mutation type of neo-epitopes were found in 119 of 147 patients, with an average of 4.34 INDEL mutations presented by MHC Class I and 0.86 INDEL mutations presented by MHC Class II molecule HLA DRB1 in every patient. Our results support the feasibility of discovering individualized mutant peptides as candidates for immunodiagnosis and immunotherapy of lung adenocarcinoma. Neo-epitopes which can be presented by both MHC Class I and MHC Class II molecules are attractive targets for designing long-peptide vaccines. Note: This abstract was not presented at the meeting. Citation Format: Dapeng Zhou, Weijing Cai, Deng Pan, Tan Wen Ling, Jiaqian Wang, Caichun Zhou, Yanyan Lou. Neoantigens predicted by clonal mutation analysis in lung adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 628. doi:10.1158/1538-7445.AM2017-628