Stimulating T cell responses against patient-derived breast cancer cells with neoantigen peptide-loaded peripheral blood mononuclear cells.

Autor: Sueangoen N; Graduate Program in Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Grove H; Division of Bioinformatics and Data Management for Research, Research Group and Research Network Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Chuangchot N; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Prasopsiri J; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Rungrotmongkol T; Center of Excellence in Biocatalyst and Sustainable Biotechnology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, Thailand., Sanachai K; Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand., Darai N; ASEAN Institute for Health Development, Mahidol University, Nakon Pathom, Thailand., Thongchot S; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Suriyaphol P; Division of Bioinformatics and Data Management for Research, Research Group and Research Network Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Sa-Nguanraksa D; Division of Head Neck and Breast Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Thuwajit P; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Yenchitsomanus PT; Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Thuwajit C; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. cthuwajit@yahoo.com.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Feb 13; Vol. 73 (3), pp. 43. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1007/s00262-024-03627-3
Abstrakt: Breast cancer stands as a formidable global health challenge for women. While neoantigens exhibit efficacy in activating T cells specific to cancer and instigating anti-tumor immune responses, the accuracy of neoantigen prediction remains suboptimal. In this study, we identified neoantigens from the patient-derived breast cancer cells, PC-B-142CA and PC-B-148CA cells, utilizing whole-genome and RNA sequencing. The pVAC-Seq pipeline was employed, with minor modification incorporating criteria (1) binding affinity of mutant (MT) peptide with HLA (IC 50 MT) ≤ 500 nm in 3 of 5 algorithms and (2) IC 50 wild type (WT)/MT > 1. Sequencing results unveiled 2513 and 3490 somatic mutations, and 646 and 652 non-synonymous mutations in PC-B-142CA and PC-B-148CA, respectively. We selected the top 3 neoantigens to perform molecular dynamic simulation and synthesized 9-12 amino acid neoantigen peptides, which were then pulsed onto healthy donor peripheral blood mononuclear cells (PBMCs). Results demonstrated that T cells activated by ADGRL1 E274K , PARP1 E619K , and SEC14L2 R43Q peptides identified from PC-B-142CA exhibited significantly increased production of interferon-gamma (IFN-γ), while PARP1 E619K and SEC14L2 R43Q peptides induced the expression of CD107a on T cells. The % tumor cell lysis was notably enhanced by T cells activated with MT peptides across all three healthy donors. Moreover, ALKBH6 V83M and GAA I823T peptides from PC-B-148CA remarkably stimulated IFN-γ- and CD107a-positive T cells, displaying high cell-killing activity against target cancer cells. In summary, our findings underscore the successful identification of neoantigens with anti-tumor T cell functions and highlight the potential of personalized neoantigens as a promising avenue for breast cancer treatment.
(© 2024. The Author(s).)
Databáze: MEDLINE
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