Abstract 4077: T cell targeting with PD-1-selective immune cell engagers based on GlycoConnect™ (GC™-ICEs) show excellent efficacy and tolerability

Abstract

Listen

Translate article

Abstract Engagement of T cell cells to harness a patient’s immune system is a promising approach in immuno-oncology. An immunocytokine, i.e. a tumor-targeting antibody (fragment) genetically fused to an immunostimulatory cytokine, is specifically designed for this purpose. Fusion antibody-immunocytokines, based on molecular architectures generated by a variant of DNA recombinant technologies, have recently entered the clinic. Earlier we have demonstrated how GlycoConnect™, a site-specific conjugation technology anchoring on the native antibody glycan1, can be applied for attachment of various cytokines, including RLI or IL-15, without prior antibody engineering. The immunostimulatory activity of these GlycoConnect™ immune cell engagers (GC™-ICEs) can be modulated by tailoring linker design and payload stoichiometry. In this presentation, we demonstrate the GC™-ICE with either IL-15 or RLI can be applied to selective targeting of T cells, based on PD-1-selective binding and activation, using either protease-sensitive or non-cleavable linkers. We will show how such T cell targeting can be achieved leading to significant tumor volume reductions in syngeneic mouse models. Moreover, we have found that the GC-ICE™ can be applied without inducing systemic immune activation, thereby displaying a promising therapeutic index. In vitro and in vivo studies will be presented to showcase the biological activity of these GC™-ICEs in comparison to conventional immunocytokines obtained via genetic engineering.1Wijdeven et al., Enzymatic glycan remodeling-metal free click (GlycoConnect™) provides homogenous antibody-drug conjugates with improved stability and therapeutic index without sequence engineering. mAbs 2022, 14, DOI: 10.1080/19420862.2022.2078466. Citation Format: Remon van Geel, Mick Verhagen, Elias Post, Willem Vugs, Sorraya Popal, Sander van Berkel, Floris van Delft. T cell targeting with PD-1-selective immune cell engagers based on GlycoConnect™ (GC™-ICEs) show excellent efficacy and tolerability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4077.