Abstract 4280: Utilizing a selective agonist of the intermediate-affinity IL-2 receptor with an improved pharmacokinetic profile leads to an enhanced immunostimulatory response With reduced toxicity in mice

Abstract

Abstract RDB 1450 is an engineered fusion protein which selectively activates the intermediate-affinity IL-2 receptor present on NK cells and memory CD8 T cells. In rodents, RDB 1450 has a half-life of 6-8 hours, compared to a half-life of minutes for recombinant human IL-2 (rhIL-2). Repeat daily dosing (QD) of RDB 1450 in mice results in marked expansion of NK cells and CD8+CD44high T cells, with minimal expansion of CD4+ regulatory T cells (Tregs). Higher QD doses elicit more pronounced effector cell expansion with modest pulmonary edema. TID delivery of the same total daily dose of RDB 1450 enhances the immunological responses in the absence of pulmonary edema. These results suggest that prolonged delivery of reduced concentrations of RDB 1450 drive the desired immune responses with improved tolerability. In contrast, high circulating concentrations of rhIL-2 are required to stimulate effector cells due to its preferential activation of Tregs at lower concentrations. The selectivity profile and favorable pharmacokinetics of RDB 1450 highlight its potential as a novel, differentiated immunotherapeutic agent for the treatment of cancer. Citation Format: Heather C. Losey, Jared E. Lopes, Reginald L. Dean, Heather Flick, Madison Gomes, Michael R. Huff, Rosemarie A. Moroso, Lei Sun, Chunhua Wang, Julie F. Waters, Juan C. Alvarez. Utilizing a selective agonist of the intermediate-affinity IL-2 receptor with an improved pharmacokinetic profile leads to an enhanced immunostimulatory response With reduced toxicity in mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4280. doi:10.1158/1538-7445.AM2015-4280