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Proteogenomic analysis unveils the HLA Class I presented immunopeptidome in melanoma and EGFR mutant lung adenocarcinoma

By Yue A. Qi, Tapan K. Maity, Constance M. Cultraro, Vikram Misra, Xu Zhang, Catherine Ade, Shaojian Gao, David Milewski, Khoa D. Nguyen, Mohammad H. Ebrahimabadi, Ken-ichi Hanada, Javed Khan, Cenk Sahinalp, James C. Yang, Udayan Guha

Posted 05 Aug 2020
bioRxiv DOI: 10.1101/2020.08.04.236331

Immune checkpoint inhibitor and adoptive lymphocyte transfer-based therapies have shown great therapeutic potential for cancers with high tumor mutation burden (TMB). Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class I-presented peptides in both melanoma, a hot tumor with high TMB, and EGFR mutant lung adenocarcinoma, a cold tumor with low TMB. We identified several classes of neopeptides, including mutated neoantigens and more than 1000 post-translationally modified peptides representing 58 different PTMs. We constructed a cancer germline (CG) antigen database with 285 antigens and identified 42 Class I-presented CG antigens. Finally, we developed a non-canonical peptide discovery pipeline to identify 44 lncRNA-derived peptides and validated Class I binding for select neopeptides. We provide direct evidence of HLA Class I presentation of a large number of neopeptides for potential vaccine or adoptive cell therapy in melanoma and mutant EGFR lung cancer. ### Competing Interest Statement U.G is a current employee of Bristol Myers Squibb. U.G. has a Clinical Trial Agreement with AstraZeneca and received research funding from AstraZeneca and Aurigene.

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