Coupling IL-2 with IL-10 to mitigate toxicity and enhance antitumor immunity.

ABSTRACT: Wild-type interleukin (IL)-2 induces anti-tumor immunity and toxicity, predominated by vascular leak syndrome (VLS) leading to edema, hypotension, organ toxicity, and regulatory T cell (Treg) expansion. Efforts to uncouple IL-2 toxicity from its potency have failed in the clinic. We hypothesize that IL-2 toxicity is driven by cytokine release syndrome (CRS) followed by VLS and that coupling IL-2 with IL-10 will ameliorate toxicity. Our data, generated using human primary cells, mouse models, and non-human primates, suggest that coupling of these cytokines prevents toxicity while retaining cytotoxic T cell activation and limiting Treg expansion. In syngeneic murine tumor models, DK2¹⁰ epidermal growth factor receptor (EGFR), an IL-2/IL-10 fusion molecule targeted to EGFR via an a

SUBMITTER: Ahn JJ 

PROVIDER: S-EPMC12432382 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature