Abstract 4281: Determination of the Relative Potency of a Selective Agonist of the Intermediate-Affinity IL-2 Receptor on Lymphocytes from Human, Cynomolgus Monkey and Mouse

Abstract

Abstract RDB 1450 is an engineered fusion protein designed to selectively activate the intermediate-affinity IL-2 receptor versus the high-affinity IL-2 receptor. The potencies of RDB 1450 and IL-2 for activation of distinct subsets of effector and regulatory lymphocytes from murine, non-human primate and human donors were determined. Splenocytes isolated from mice or leukocytes isolated from human or cyno blood were stimulated with either RDB 1450 or IL-2. Multicolor flow cytometry was used to identify distinct subpopulations and the extent of phosphorylation of STAT5 was measured. Whereas IL-2 is 2-3 orders of magnitude more potent on immunosuppressive Tregs relative to NK cells and memory CD8 T cells, RDB 1450 induces activation of NK cells, memory CD8 T cells and Tregs at comparable concentrations within each species. The non-differentiated potency of RDB 1450 on the lymphocyte subpopulations examined suggests that its effects are mediated through the intermediate affinity receptors even on CD25-expressing Tregs. The preferential activation of Tregs by IL-2 may lead to immunosuppression and limit its antitumor efficacy. In contrast, RDB 1450 does not exhibit the same preference for Treg activation and is expected to be more effective in driving antitumor immune responses. These results highlight the differentiated immunological profile of RDB 1450 and support its potential as a novel human immunotherapy. Citation Format: Emily E. Rosentrater, Heather Flick, Jared E. Lopes, Heather C. Losey, Chunhua Wang, Juan C. Alvarez. Determination of the Relative Potency of a Selective Agonist of the Intermediate-Affinity IL-2 Receptor on Lymphocytes from Human, Cynomolgus Monkey and Mouse. [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 4281. doi:10.1158/1538-7445.AM2015-4281