Abstract 2121: MAIT engagers: Providing a large therapeutic window for the treatment of solid tumors

作者：Simon Plyte, Marie Fraudeau, Dorothee Winterberg, Claire Germain, Camille Rouseau, Gaetano Sodaro, Maxime Audin, Alexandre Ivagnès, Hans-Heiner Oberg, Pierre-Emmanuel Gerard, Matthias Peipp, Daniela Wesch, Julie Prigent · 发表于：Cancer Research · 年份：2025 · DOI：10.1158/1538-7445.am2025-2121 · 被引用次数：1 · 研究领域：Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery、Cancer Research and Treatments

Abstract Background: MAIT cells are an abundant subset of non-conventional T-cells with potent cytotoxic capacity that are resident in most tissues and solid tumors. MAIT cell engagers are bispecific antibodies that are able to simultaneously bind the MAIT cell TCR and a tumor associated antigen, creating an immunological synapse, resulting in efficient elimination of cancer cells. These MAIT engagers only bind and activate MAIT cells and, at difference to classical CD3 engagers, do not cause cytokine release or activate regulatory T cells offering the promise of better safety and efficacy than CD3 engagers. Methods: Using the Biomunex proprietary BiXAb platform, bispecific, tetravalent antibodies were generated that target the MAIT iTCR (invariant T cell receptor) and the HER2 tumor associated antigen. MAIT-cell activation, proliferation and degranulation were followed by gating on MAIT cells within a purified CD8 cell population. Tumor cell lines (varying [HER2]) were co-cultured with MAIT cells and the BiXAbs in several cytotoxic assays (evaluated by Chromium release). Cytokine release was assessed by Legend Plex assays or ELISA. Regulatory T cells were enriched from PBMCs. Cytotoxicity of tumor-resident MAITs, from fresh patient samples, was determined by impedance measurements and in patient derived 3D organoids by imaging (The Hub organoids). Cytokine levels in serum of Cynomolgus monkeys was measured by Legend plex. Results: MAIT engagers induce the rapid activation, p...