Abstract 1866: D02, a novel, non-blocking antibody targeting IL2RA, exhibits significant anti-tumor activity in IL2RA-humanized mice

Abstract

Abstract Regulatory T cells, or Tregs, are a subset of CD4+ T cells that negatively regulate immune responses to promote their resolution and protect against autoimmunity. Infiltration of Tregs in the tumor microenvironment (TME), and a low ratio of effector T cells to Tregs, is frequently associated with tumor progression and poor prognosis. The alpha subunit of the IL-2 cytokine receptor (IL2RA), a component of the high-affinity IL-2 receptor along with the β and γ subunits (IL2Rβγ), is constitutively expressed on Tregs and transiently expressed on effector T cells. IL-2 is a key cytokine for effector T cell survival and cytolytic responses. We aimed to discover an IL2RA-targeting antibody capable of depleting Tregs but permitting IL-2 stimulation of effector T cells in the TME. We developed a fully human IgG1 antibody specific to IL2RA, D02, from our proprietary RenMab™ mice, which contain the entire human immunoglobulin variable domain. D02 binds both human and cynomolgus monkey IL2RA with high affinity without hindering IL2RA-IL-2 binding or inhibiting IL-2 signaling. To evaluate the safety and efficacy of D02 in vivo, we established a syngeneic mouse tumor model in IL2RA-humanized mice. We observed that D02 potently inhibited MC38 (colon adenocarcinoma) tumor growth at 10 mg/kg. Further studies will aim to characterize the effect of D02 on the ratio of effector T cells to Tregs in the TME. These data indicate that D02 is a novel, IL2RA-specific monoclonal antibody that uniquely exhibits significant anti-tumor activity in vivo while preserving IL-2 signaling to effector T cells. Citation Format: Shuzhen Cao, Wenjiao Zhang, Qingcong Lin. D02, a novel, non-blocking antibody targeting IL2RA, exhibits significant anti-tumor activity in IL2RA-humanized mice [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 1866.