Frontiers in immunology · 2026
Evaluating mesothelin as an immunotherapeutic target for endogenous T cells.
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Koukoulias Kiriakos, Yanagisawa Ryu, Torres Chavez Alejandro G, Papayanni Penelope G, Velazquez Yovana, Lee Hyun-Sung, Vasileiou Spyridoula, Leen Ann M
Аннотация
BACKGROUND: Mesothelin (MSLN) is a GPI-anchored cell surface glycoprotein that is overexpressed in various solid tumors, including mesothelioma, triple-negative breast cancer, colon, ovarian and pancreatic cancer, with restricted normal tissue expression.
METHODS: To explore the immunogenicity and immunotherapeutic potential of MSLN to T cells with native receptor specificity, 29 individuals of diverse HLA backgrounds were interrogated for T cell activity against MSLN.
RESULTS: Twenty one (72%) subjects (21/29) mounted a specific T cell response when repetitively challenged with MSLN antigen. Reactive cells were Th1-polarized, polyfunctional, predominantly detected in the CD8+ T cell compartment and cytotoxic toward autologous and MSLN+/HLA-matched tumor cell lines in conventional 2D in vitro assays. Furthermore, these cells produced anti-tumor effects in a novel 3D tumor spheroid model system established to evaluate the potency of reactive cells against tumors including pancreatic, cervical, and colorectal cancer and mesothelioma.
CONCLUSIONS: These preclinical findings lay the groundwork for further exploration of MSLN as a potential immunotherapeutic target for T cells via the native T cell receptor.
METHODS: To explore the immunogenicity and immunotherapeutic potential of MSLN to T cells with native receptor specificity, 29 individuals of diverse HLA backgrounds were interrogated for T cell activity against MSLN.
RESULTS: Twenty one (72%) subjects (21/29) mounted a specific T cell response when repetitively challenged with MSLN antigen. Reactive cells were Th1-polarized, polyfunctional, predominantly detected in the CD8+ T cell compartment and cytotoxic toward autologous and MSLN+/HLA-matched tumor cell lines in conventional 2D in vitro assays. Furthermore, these cells produced anti-tumor effects in a novel 3D tumor spheroid model system established to evaluate the potency of reactive cells against tumors including pancreatic, cervical, and colorectal cancer and mesothelioma.
CONCLUSIONS: These preclinical findings lay the groundwork for further exploration of MSLN as a potential immunotherapeutic target for T cells via the native T cell receptor.