Abstract A032: Advancing the allogeneic MAIT platform for targeting solid tumors

Abstract The recent FDA approvals of the first TCR-T and TIL therapies for solid tumors represent a landmark in cell therapy, breaking the fear barrier and proving that cell-based therapies can take on difficult-to-treat cancers. Despite this breakthrough, low efficacy, poor tumor migration, and the inability to resist tumor counterattack continue to limit broader application in solid cancers. Transitioning from a patient’s own cells to donor cells is the next conceptual barrier, essential for making cell therapy more accessible and affordable. Mucosal-associated invariant T (MAIT) cell-based immunotherapy offers promising potential as a next-generation solution. Unlike conventional T cell therapies, MAIT cells possess intrinsic qualities that address pressing limitations in treating solid tumors. However, translating this promise clinically has been constrained by the challenge of expanding MAIT cells to therapeutically relevant numbers. Pluri has addressed this hurdle with a novel three-dimensional (3D) bioreactor platform, employing packed-bed bioreactors to produce functional MAIT cells at scale, tailored for both autologous and allogeneic applications. Our proprietary 3D platform leverages porous scaffolds coated with extracellular matrix (ECM) proteins and immune-activating ligands, creating a biomimetic microenvironment that mimics physiological conditions and maximizes MAIT cell growth. Antigen-presenting cells (APCs) adhere to the scaffolds and, upon stimulation with the riboflavin metabolite 5-OP-RU, drive the activation and expansion of MAIT cells in a closed, automated bioreactor. This system consistently yields a highly functional, proliferative MAIT cell population, producing clinically relevant cell numbers that surpass conventional expansion techniques. Pluri’s CAR-MAIT cells have demonstrated potent anti-tumor activity with strong functional persistence in serial rechallenge and spheroid killing assays. Incorporating tumor-specific TCRs as an additional engineering approach has further shown efficacy and polyfunctionality of TCR-MAIT cells in response to diverse tumor targets. In-depth transcriptomic and membranomic profiling of placental MAIT cells reveals a unique expression profile distinct from conventional T cells. Notably, high chemokine receptor expression indicates remarkable migratory potential, essential for reaching tumors in peripheral locations. Real-time chemotaxis analysis has confirmed superior migration of MAIT cells compared to T cells toward chemokine gradients and tumor cell supernatants, addressing a key barrier in solid tumor targeting. In summary, Pluri’s MAIT cells exhibit unique biological advantages that position them to overcome key limitations of existing T and NK cell therapies. CAR-MAIT and TCR-MAIT therapies provide a compelling solution for targeting solid tumors, combining effective migration to peripheral sites with robust anti-tumor activity and persistence. Our scalable platform supports the clinical realization of MAIT cell-based therapies, opening new possibilities in treating resistant cancers. Citation Format: Adi Sharbi-Yunger, Shirley Bachar, Helena Shaked, Dorina Roberman, Eliran Ish Shalom, Ben Gelles, Sagiv Kronenfeld, Dikla Vardi, Maria Presman, Sojod Mahroum, Hila Dressler, Ilana Goor, Maya Levi Mann, Elena Kivovich, Oshrat Bassan, Nadin Sabbah, Hen Amram, Shiri Klein, Michal Lotem, Michal Sheleg, Lior Raviv, Arthur Machlenkin. Advancing the allogeneic MAIT platform for targeting solid tumors [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A032.