CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity
Name
cir-23-0636.pdf
Description
Published version
Size
5.26 MB
Format
Adobe PDF
Checksum (MD5)
8e5864f869698226bf70e070391fecd1
Author(s)
Mehta, Naveen K
Rakhra, Kavya
Meetze, Kristan A
Li, Bochong
Momin, Noor
Chang, Jason YH
Wittrup, K Dane
Baeuerle, Patrick A
Michaelson, Jennifer S
Date Issued
August 1, 2024
Journal
Cancer Immunology Research
Publisher
American Association for Cancer Research
Citation
Naveen K. Mehta, Kavya Rakhra, Kristan A. Meetze, Bochong Li, Noor Momin, Jason Y.H. Chang, K. Dane Wittrup, Patrick A. Baeuerle, Jennifer S. Michaelson; CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity. Cancer Immunol Res 1 August 2024; 12 (8): 1022–1038.
Version
Final published version
Abstract
Despite clinical evidence of antitumor activity, the development of cytokine therapies has been hampered by a narrow therapeutic window and limited response rates. Two cytokines of high interest for clinical development are interleukin 2 (IL2) and interleukin 12 (IL12), which potently synergize to promote the activation and proliferation of T cells and NK cells. However, the only approved human IL2 therapy, Proleukin, is rarely used in the clinic due to systemic toxicities, and no IL12 product has been approved to date due to severe dose-limiting toxicities. Here, we describe CLN-617, a first-in-class therapeutic for intratumoral (IT) injection that co-delivers IL2 and IL12 on a single molecule in a safe and effective manner. CLN-617 is a single-chain fusion protein comprised of IL2, leukocyte-associated immunoglobulin-like receptor 2 (LAIR2), human serum albumin (HSA), and IL12. LAIR2 and HSA function to retain CLN-617 in the treated tumor by binding collagen and increasing molecular weight, respectively. We found that IT administration of a murine surrogate of CLN-617, mCLN-617, eradicated established treated and untreated tumors in syngeneic models, significantly improved response to anti-PD1 checkpoint therapy, and generated a robust abscopal response dependent on cellular immunity and antigen cross-presentation. CLN-617 is being evaluated in a clinical trial in patients with advanced solid tumors (NCT06035744).
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
10.1158/2326-6066.cir-23-0636
