Abstract B005: FPT155, a novel therapeutic CD80-Fc fusion protein with potent antitumor activity in preclinical models

Abstract

Abstract Optimal activation of T cells requires both antigen-specific signaling and induction of costimulatory pathways. Costimulatory pathways are upregulated by foreign antigenic challenge but are not active in the normal immune state, thus maintaining peripheral tolerance to self-antigens. The absence of costimulatory signaling may likewise play a role in tolerance to cancer cells. Five Prime has developed a CD80 (B7.1) extracellular domain (ECD)-Fc fusion protein (FPT155) as a costimulatory molecule that can stimulate T-cell activation and break tumor immune tolerance. In vitro studies show that FPT155 induces T-cell activation and cytokine production via CD28. FPT155 activity requires T-cell receptor engagement, which indicates that FPT155 is not a CD28 “superagonist” that can drive T-cell activation independently of antigenic stimulation. To investigate the impact of CD80-Fc in preclinical models, we generated murine FPT155 (mFPT155), a surrogate fusion protein, composed of the mouse CD80 ECD fused with the murine Fc region of IgG2a. mFPT155 is well tolerated in mice and has potent efficacy in syngeneic tumor models, including the induction of complete tumor regression in the CT26 model. mFPT155 promotes the infiltration of T cells into the tumor core and increases the effector T:Treg ratio, thus inducing a favorable microenvironment for an effective antitumor immune response. Furthermore, combination of mFPT155 and anti-PD1 therapy leads to stronger antitumor efficacy compared to either therapy alone. Together these results indicate that mFPT155 is a potent T-cell costimulator with strong antitumor activity in mouse tumor models. We are currently performing IND-enabling studies and plan to initiate a clinical study with FPT155 in 2018. Citation Format: Susannah D. Barbee, Barbara Sennino, Jacqueline De La Torre, Monica Macal, Quinn Walker, Marc R. Jabon, Amanda Chen, David A. Busha, Margaret Best, Kristen L. Pierce, Luis Borges, Kevin P. Baker, Thomas Brennan. FPT155, a novel therapeutic CD80-Fc fusion protein with potent antitumor activity in preclinical models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B005.