Abstract 33: Development of a humanized mouse model for γδT cells

Unconventional T cells such as gamma delta (γδ) T cells have garnered significant interest in cancer immunotherapy due to their potent anti-tumor properties including strong cytotoxic capabilities in hematological malignancies and their ability to recognize a broad range of tumor antigens independent of the classical major histocompatibility complex (MHC) molecules. Given the interest in engaging these immune cell populations in cancer therapy, we established a new in vivo humanized mouse model through the adoptive transfer of human γδT cells to support this emerging area of therapeutic interest. This model was created by transplanting γδT cells sorted from PBMC donors into Fc-resolv huIL15 NOG (functional knock-out of murine Fcγ receptors to minimize the confounding impact of mouse immune cells) mice, genetically engineered to express human IL-15. We demonstrate that various γδT cell populations, including Vδ1 and Vδ2, can be successfully maintained over a long period of time, preserving the expression of critical functional biomarkers such as NKG2D, CD69 or CD16, under various engraftment conditions. Additionally, we showed that hu γδT cells display functional engagement in vivo, achieving high efficacy with epcoritamab (CD20-CD3 Ab) against disseminated tumors in the hu γδT cell adoptive transfer mouse model. Citation Format: Lydia Blot, Lopes Joaquim, Emerson Serres, Vanessa Croize, Hervé Barret, Pauline Rettman, Clément Barjon, Dorothee Bourges, Antoine Lhermitte, Valéria Fantin, Sukhvinder Sidhu, Loreley Calvet. Development of a humanized mouse model for γδT cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 33.