Abstract 4425: GlycoConnect™ immune cell engagers (GC™-ICEs). A non-genetic approach to targeted IL-15 immunotherapy

Abstract

Abstract Engagement of T cell or NK 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-IL-15 immunocytokines, based on a variety of molecular architectures, are currently finding their way to the clinic with promising results. Here we demonstrate how GlycoConnect™, a site-specific conjugation technology anchoring on the native antibody glycan, can be applied for attachment of IL-15 without prior antibody engineering. Moreover, the immunostimulatory activity of these GlycoConnect™ immune cell engagers (GC™-ICEs) can be modulated by tailoring linker design and payload stoichiometry. In particular, we demonstrate how a protease-cleavable mAb-IL-15 conjugate can be used to prevent systemic activation of the immune system, leading to a significantly improved therapeutic index in rodent models. 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. Citation Format: Remon van Geel, Floris van Delft. GlycoConnect™ immune cell engagers (GC™-ICEs). A non-genetic approach to targeted IL-15 immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4425.