Abstract LB175: APX601, a Potent TNFR2 Antagonist as a Novel and Promising Approach to Reverse Tumor Immune Suppression

Abstract

Abstract A key barrier to effective immunotherapy for cancer is the immunosuppressive tumor microenvironment (TME) characterized by infiltrating regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). While depletion of immune-suppressive cells is a promising cancer immunotherapy strategy, current approaches are ineffective due to lack of specificity and safety concerns. Tumor Necrosis Factor Receptor 2 (TNFR2) is emerging as a novel, selective target to overcome immunosuppression in the TME. Here we present APX601 as a potent Treg and myeloid suppressive cell inhibitor. APX601 is a humanized IgG1 antibody to TNFR2 generated using APXiMAB™, Apexigen's proprietary antibody platform. APX601 selectively binds human and monkey TNFR2, blocks the binding of TNFR2 to TNF-α and depletes TNFR2-expressing Treg and tumor cells in vitro. In addition to depleting suppressive cells, APX601 can also reverse MDSC and Tregs mediated immune suppression. In human TNFR2 knock-in syngeneic mouse tumor models CT26 and MC38, treatment with APX601 results in significant tumor growth inhibition both as a single agent and in combination with anti-PD-1. Thus, APX601 is a potent antagonist antibody against TNFR2 with the ability to reverse immune suppression in TME and inhibit tumor growth. APX601 was evaluated in a repeat dose range finding toxicology study in monkeys and demonstrated a good safety profile when administered up to 100mg/kg. These data strongly support the development of APX601 as a novel therapeutic approach for reversing tumor immune suppression and for the treatment solid tumors. Citation Format: Sushma Krishnan, Ryan Alvarado, George Huang, Xiaodong Yang, Erin L. Filbert. APX601, a Potent TNFR2 Antagonist as a Novel and Promising Approach to Reverse Tumor Immune Suppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB175.