Abstract 1633: MAIT engagers: Avoiding Treg suppression to deliver stronger activity in solid tumors

作者：Simon Plyte, Marie Fraudeau, Dorothee Winterberg, Claire Germain, Camille Rousseau, Maxime Audin, Alexandre Ivagnès, Sothea Touch Dumoitier, Sarah Ducellier, Lise Fenou, Hans Heinrich Oberg, Pierre Emmanuel Gerard, Isabelle Teulon, Daniela Wesch, Matthias Peipp, Julie Prigent · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-1633 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers

Abstract MAIT engagers are part of the immune cell engager drug modality and specifically target Mucosal Associated Invariant T cells (MAITs) via their unique T cell receptor (TCR) and tether them to cancer cells, via a tumor antigen, to elicit MAIT-mediated cell death. MAIT cells are an abundant cytotoxic subset of non-conventional T cells that are present in blood and all major organs and are particularly enriched in barrier tissues. Classical CD3 engagers activate all T cell subsets, including the regulatory T-cell (T-regs) population whose activation in the tumor microenvironment (TME) will dampen the intended cytotoxicity of the CD8 cytotoxic T cells and will limit CD3 engager efficacy. Unlike CD3 engagers, MAIT engagers only activate MAIT cells and do not cause increased immune suppression via T-reg activation or cytokine release syndrome (CRS) via general CD4 T cell activation. MAIT engagers were generated using Biomunex’s proprietary bispecific, tetravalent antibody platform, BiXAb. MAIT-cell activation, proliferation, degranulation and cytotoxicity assays were established in co-culture between tumor cells, immune cell subsets (CD8 or PBMCs) and BiXAb MAIT engagers. Analysis of activation, degranulation and proliferation was followed by FACs whilst cytotoxicity was assessed by chromium release. Regulatory T cells were enriched from PBMCs and used in co-culture assays to assess CD8 T cell repression as judged by IL-2 release. General cytokine release was measured by Le...