Prioritizing Candidate Peptides for Cancer Vaccines Through Predicting Peptide Presentation by HLA-I Proteins

• Published in: Biometrics Vol. 79; no. 3; pp. 2664 - 2676
• Main Authors: Zhou, Laura Y., Zou, Fei, Sun, Wei
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2023
• Subjects: Antigens; Antigens, Neoplasm - genetics; Cancer; Cancer vaccines; Cancer Vaccines - chemistry; Cell surface; Histocompatibility antigen HLA; HLA antigens; HLA Antigens - genetics; Humans; Immune response; Immune system; Immunogenicity; Mass spectrometry; Mass spectroscopy; Melanoma; Melanoma - genetics; Mixtures; Mutation; Neoantigens; Neoplasms - genetics; Neural networks; Peptides; Peptides - chemistry; Peptides - genetics; Tumor cells; Tumors; Vaccines; melanoma; neoantigens; mixture model; cancer vaccine; neural network; peptide-HLA association
• ISSN: 0006-341X; 1541-0420; 1541-0420
• DOI: 10.1111/biom.13717

Cancer (treatment) vaccines that are made of neoantigens, or peptides unique to tumor cells due to somatic mutations, have emerged as a promising method to reinvigorate the immune response against cancer. A key step to prioritizing neoantigens for cancer vaccines is computationally predicting which neoantigens are presented on the cell surface by a human leukocyte antigen (HLA). We propose to address this challenge by training a neural network using mass spectrometry (MS) data composed of peptides presented by at least one of several HLAs of a subject. We embed the neural network within a mixture model and train the neural network by maximizing the likelihood of the mixture model. After evaluating our method using data sets where the peptide presentation status was known, we applied it to analyze somatic mutations of 60 melanoma patients and identified a group of neoantigens more immunogenic in tumor cells than in normal cells. Moreover, neoantigen burden estimated by our method was significantly associated with a measurement of the immune system activity, suggesting these neoantigens could induce an immune response.