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Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells.
Thongchot, Suyanee; Aksonnam, Krittaya; Prasopsiri, Jaturawitt; Warnnissorn, Malee; Sa-Nguanraksa, Doonyapat; O-Charoenrat, Pornchai; Thuwajit, Peti; Yenchitsomanus, Pa-Thai; Thuwajit, Chanitra.
Afiliación
  • Thongchot S; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
  • Aksonnam K; Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
  • Prasopsiri J; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
  • Warnnissorn M; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
  • Sa-Nguanraksa D; Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
  • O-Charoenrat P; Division of Head Neck and Breast Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
  • Thuwajit P; Breast Center, MedPark Hospital, Bangkok, 10110, Thailand.
  • Yenchitsomanus PT; Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
  • Thuwajit C; Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
BMC Med ; 22(1): 400, 2024 Sep 18.
Article en En | MEDLINE | ID: mdl-39294656
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteínas de Unión al ARN / Proteínas Ligadas a GPI / Neoplasias de la Mama Triple Negativas / Mesotelina / Nucleolina Límite: Adult / Female / Humans / Middle aged Idioma: En Revista: BMC Med Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteínas de Unión al ARN / Proteínas Ligadas a GPI / Neoplasias de la Mama Triple Negativas / Mesotelina / Nucleolina Límite: Adult / Female / Humans / Middle aged Idioma: En Revista: BMC Med Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido