Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells
Issued Date
2024-09-18
Resource Type
eISSN
17417015
Scopus ID
2-s2.0-85204418255
Pubmed ID
39294656
Journal Title
BMC medicine
Volume
22
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
BMC medicine Vol.22 No.1 (2024) , 400
Suggested Citation
Thongchot S., Aksonnam K., Prasopsiri J., Warnnissorn M., Sa-nguanraksa D., O-Charoenrat P., Thuwajit P., Yenchitsomanus P.T., Thuwajit C. Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells. BMC medicine Vol.22 No.1 (2024) , 400. doi:10.1186/s12916-024-03625-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/101369
Title
Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells
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Corresponding Author(s)
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Abstract
BACKGROUND: Triple-negative breast cancer (TNBC), known for its aggressiveness and limited treatment options, presents a significant challenge. Adoptive cell transfer, involving the ex vivo generation of antigen-specific T cells from peripheral blood mononuclear cells (PBMCs), emerges as a promising approach. The overexpression of mesothelin (MSLN) and nucleolin (NCL) in TNBC samples underscores their potential as targets for T cell therapy. This study explored the efficacy of multi-peptide pulsing of PBMCs to generate MSLN/NCL-specific T cells targeting MSLN+/NCL+ TNBC cells. METHODS: TNBC patient samples were confirmed for both MSLN and NCL expression via immunohistochemistry. Synthesized MSLN and NCL peptides were combined and administered to activate PBMCs from healthy donors. The cancer-killing ability of the resultant T cells was assessed using crystal violet staining, and their subtypes and cytotoxic cytokines were characterized through flow cytometry and cytokine bead array. RESULTS: Findings showed that 85.3% (127/149) of TNBC cases were positive for either MSLN or NCL, or both; with single positivity rates for MSLN and NCL of 14.1% and 28.9%, respectively. MSLN and NCL peptides, with high binding affinity for HLA-A*02, were combined and introduced to activated PBMCs from healthy donors. The co-pulsed PBMCs significantly induced TEM and TEMRA CD3+/CD8+ T cells and IFN-γ production, compared to single-peptide pulsed or unpulsed conditions. Notably, MSLN/NCL-specific T cells successfully induced cell death in MSLN+/NCL+ MDA-MB-231 cells, releasing key cytotoxic factors such as perforin, granzymes A and B, Fas ligand, IFN-γ, and granulysin. CONCLUSIONS: These findings serve as a proof-of-concept for using multiple immunogenic peptides as a novel therapeutic approach in TNBC patients.