Data from CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity

• DOI: 10.1158/2326-6066.c.7380038.v1
• Publication Date: 2024-08-01T14:24:13Z
• Authors: Naveen K. Mehta; Kavya Rakhra; Kristan A. Meetze; Bochong Li; Noor Momin; Jason Y.H. Chang; K. Dane Wittrup; Patrick A. Baeuerle; Jennifer S. Micha...

<div>Abstract<p>Despite clinical evidence of antitumor activity, the development cytokine therapies has been hampered by a narrow therapeutic window and limited response rates. Two cytokines high interest for are interleukin 2 (IL2) 12 (IL12), which potently synergize to promote activation proliferation T cells NK cells. However, only approved human IL2 therapy, Proleukin, is rarely used in clinic due systemic toxicities, no IL12 product date severe dose-limiting toxicities. Here, we describe CLN-617, first-in-class intratumoral (IT) injection that co-delivers on single molecule safe effective manner. CLN-617 single-chain fusion protein comprised IL2, leukocyte-associated immunoglobulin-like receptor (LAIR2), serum albumin (HSA), IL12. LAIR2 HSA function retain treated tumor binding collagen increasing molecular weight, respectively. We found IT administration murine surrogate mCLN-617, eradicated established untreated tumors syngeneic models, significantly improved anti-PD1 checkpoint generated robust abscopal dependent cellular immunity antigen cross-presentation. being evaluated trial patients with advanced solid (NCT06035744).</p></div>