Streamlined selection of cancer antigens for vaccine development through integrative multi-omics and high-content cell imaging

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Abstract

Identification of tumor antigens that induce cytotoxic T lymphocytes (CTLs) is crucial for cancer-vaccine development. Despite their predictive ability, current algorithmic approaches and human leukocyte antigen (HLA)-peptidomic analysis allow limited selectivity. Here, we optimized a method to rapidly screen and identify highly immunogenic epitopes that trigger CTL responses. We used a combined application of this method involving immune-specific signature analysis and HLA-associated peptidomics using samples from six patients with triple-negative breast cancer (TNBC) in order to select immunogenic HLA epitopes for in vitro testing. Additionally, we applied high-throughput imaging at the single-cell level in order to confirm the immunoreactivity of the selected peptides. The results indicated that this method enabled identification of promising CTL peptides capable of inducing antitumor immunity. This platform combining high-resolution computational analysis, HLA-peptidomics, and high-throughput immunogenicity testing allowed rapid and robust identification of highly immunogenic epitopes and represents a powerful technique for cancer-vaccine development.

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Most cited references 33

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Author and article information

Contributors

Ki-Cheol Han: biolord@kist.re.kr

Cheolju Lee: clee270@kist.re.kr

Mihue Jang: mihue@kist.re.kr

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 3 April 2020

Publication date PMC-release: 3 April 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 5885

Affiliations

[1 ]ISNI 0000000121053345, GRID grid.35541.36, Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, ; Seoul, 02792 Republic of Korea

[2 ]ISNI 0000 0004 0532 3933, GRID grid.251916.8, Department of Biological Sciences, College of Natural Sciences, , Ajou University, ; Suwon, 16499 Republic of Korea

[3 ]ISNI 0000 0001 0840 2678, GRID grid.222754.4, College of Life Science and Biotechnology, , Korea University, ; 145 Anam-ro, Seongbuk-gu, Seoul, 02841 Republic of Korea

[4 ]ISNI 0000 0004 0533 4667, GRID grid.267370.7, Department of Pathology, Asan Medical Center, , University of Ulsan College of Medicine, ; 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Republic of Korea

[5 ]ISNI 0000 0001 0842 2126, GRID grid.413967.e, Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, , University of Ulsan College of Medicine, Asan Medical Center, ; Seoul, 05505 Republic of Korea

[6 ]ISNI 0000 0001 0840 2678, GRID grid.222754.4, Oncology/Hematology, Department of Internal medicine, , Korea University College of medicine, Seongbuk-Gu, ; Seoul, 02841 Republic of Korea

[7 ]ISNI 0000 0001 2171 7818, GRID grid.289247.2, Department of Converging Science and Technology, , KHU-KIST, Kyung Hee University, ; Seoul, 02447 Republic of Korea

Article

Publisher ID: 62244

DOI: 10.1038/s41598-020-62244-z

PMC ID: 7125174

PubMed ID: 32245999

SO-VID: 63f23d01-e840-49d4-a445-3843cda42714

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.