PMID- 32245999 OWN - NLM STAT- MEDLINE DCOM- 20201125 LR - 20210403 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Apr 3 TI - Streamlined selection of cancer antigens for vaccine development through integrative multi-omics and high-content cell imaging. PG - 5885 LID - 10.1038/s41598-020-62244-z [doi] LID - 5885 AB - 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. FAU - Han, Ki-Cheol AU - Han KC AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea. biolord@kist.re.kr. FAU - Park, Daechan AU - Park D AD - Department of Biological Sciences, College of Natural Sciences, Ajou University, Suwon, 16499, Republic of Korea. FAU - Ju, Shinyeong AU - Ju S AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea. FAU - Lee, Young Eun AU - Lee YE AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea. AD - College of Life Science and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. FAU - Heo, Sun-Hee AU - Heo SH AD - Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. AD - 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. FAU - Kim, Young-Ae AU - Kim YA AD - Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. FAU - Lee, Ji Eun AU - Lee JE AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea. FAU - Lee, Yuna AU - Lee Y AD - College of Life Science and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. FAU - Park, Kyong Hwa AU - Park KH AD - Oncology/Hematology, Department of Internal medicine, Korea University College of medicine, Seongbuk-Gu, Seoul, 02841, Republic of Korea. FAU - Park, Se-Ho AU - Park SH AD - College of Life Science and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. FAU - Lee, Hee Jin AU - Lee HJ AD - Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. AD - 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. FAU - Lee, Cheolju AU - Lee C AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea. clee270@kist.re.kr. AD - Department of Converging Science and Technology, KHU-KIST, Kyung Hee University, Seoul, 02447, Republic of Korea. clee270@kist.re.kr. FAU - Jang, Mihue AU - Jang M AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea. mihue@kist.re.kr. AD - Department of Converging Science and Technology, KHU-KIST, Kyung Hee University, Seoul, 02447, Republic of Korea. mihue@kist.re.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200403 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (HLA Antigens) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Antigens, Neoplasm/*immunology MH - Cancer Vaccines/*immunology MH - Gas Chromatography-Mass Spectrometry MH - HLA Antigens/immunology MH - High-Throughput Screening Assays MH - Humans MH - Proteomics/methods MH - Receptors, Antigen, T-Cell/immunology MH - Triple Negative Breast Neoplasms/immunology PMC - PMC7125174 COIS- KIST has filed a patent on which M.J., C.L., K.H., J.L. and S.J. are listed as inventors. The other authors declare no competing financial interest. EDAT- 2020/04/05 06:00 MHDA- 2020/11/26 06:00 PMCR- 2020/04/03 CRDT- 2020/04/05 06:00 PHST- 2019/11/04 00:00 [received] PHST- 2020/03/09 00:00 [accepted] PHST- 2020/04/05 06:00 [entrez] PHST- 2020/04/05 06:00 [pubmed] PHST- 2020/11/26 06:00 [medline] PHST- 2020/04/03 00:00 [pmc-release] AID - 10.1038/s41598-020-62244-z [pii] AID - 62244 [pii] AID - 10.1038/s41598-020-62244-z [doi] PST - epublish SO - Sci Rep. 2020 Apr 3;10(1):5885. doi: 10.1038/s41598-020-62244-z.