IL-2/IL-12-based fusion protein CLN-617

A single-chain fusion protein composed of the human cytokine interleukin-2 (IL-2), the collagen-binding domain leukocyte-associated immunoglobulin-like receptor 2 (LAIR2), linked, through glycine/serine linkers, to human serum albumin (HSA) and human IL-12, with potential immunoregulatory and antineoplastic activities. Upon intratumoral (IT) administration of CLN-617, both the IL-2 and IL-12 moieties bind to their respective receptors expressed on CD8+ T cells and natural killer (NK) cells in the tumor microenvironment (TME), thereby activating IL-2- and IL-12-mediated signaling. This synergistically activates and expands CD8+ T cells and NK cells and leads to cytolytic immune responses against tumor cells, which kills tumor cells and inhibits tumor cell proliferation, and triggers systemic anti-tumor immunity. LAIR2 and HSA specifically retain CLN-617 in the injected tumor by binding collagen and increasing molecular weight (MW), respectively. The specific delivery and retention into the tumor increase efficacy of CLN-617 while sparing the unwanted toxic effects of IL-2 and IL-12.