Stimulating T cell responses against patient-derived breast cancer cells with neoantigen peptide-loaded peripheral blood mononuclear cells
Issued Date
2024-03-01
Resource Type
ISSN
03407004
eISSN
14320851
Scopus ID
2-s2.0-85185107118
Pubmed ID
38349410
Journal Title
Cancer Immunology, Immunotherapy
Volume
73
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cancer Immunology, Immunotherapy Vol.73 No.3 (2024)
Suggested Citation
Sueangoen N., Grove H., Chuangchot N., Prasopsiri J., Rungrotmongkol T., Sanachai K., Darai N., Thongchot S., Suriyaphol P., Sa-Nguanraksa D., Thuwajit P., Yenchitsomanus P.T., Thuwajit C. Stimulating T cell responses against patient-derived breast cancer cells with neoantigen peptide-loaded peripheral blood mononuclear cells. Cancer Immunology, Immunotherapy Vol.73 No.3 (2024). doi:10.1007/s00262-024-03627-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97352
Title
Stimulating T cell responses against patient-derived breast cancer cells with neoantigen peptide-loaded peripheral blood mononuclear cells
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Corresponding Author(s)
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Abstract
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 (IC50 MT) ≤ 500 nm in 3 of 5 algorithms and (2) IC50 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 ADGRL1E274K, PARP1E619K, and SEC14L2R43Q peptides identified from PC-B-142CA exhibited significantly increased production of interferon-gamma (IFN-γ), while PARP1E619K and SEC14L2R43Q 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, ALKBH6V83M and GAAI823T 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.