Back to Search
Start Over
An engineered immunocytokine with collagen affinity improves the tumor bioavailability, tolerability, and therapeutic efficacy of IL-2.
- Source :
-
Cell reports. Medicine [Cell Rep Med] 2023 Nov 21; Vol. 4 (11), pp. 101289. - Publication Year :
- 2023
-
Abstract
- The clinical utility of human interleukin-2 (hIL-2) is limited by its short serum half-life, preferential activation of regulatory T (T <subscript>Reg</subscript> ) over immune effector cells, and dose-limiting toxicities. We previously engineered F10 immunocytokine (IC), an intramolecularly assembled cytokine/antibody fusion protein that linked hIL-2 to an anti-IL-2 antibody (denoted F10) that extended IL-2 half-life and augmented the immune effector to T <subscript>Reg</subscript> ratio. Here, we leveraged molecular engineering to improve the anti-tumor therapeutic efficacy and tolerability of F10 IC by developing an iteration, denoted F10 IC-CBD (collagen binding domain), designed for intratumoral administration and in situ retention based on collagen affinity. F10 IC-CBD retained IL-2 bioactivity exclusively in the tumor and eliminated IL-2-associated toxicities. Furthermore, F10 IC exhibited potent single-agent therapeutic efficacy and synergy with systemic immune checkpoint blockade and elicited an abscopal response in mouse tumors models. This engineered fusion protein presents a prototype for the design of intratumoral therapies.<br />Competing Interests: Declaration of interests Johns Hopkins University has filed intellectual property (WO2020264321A1) entitled “Methods and materials for targeted expansion of immune effector cells” that covers compound F10 IC as well as related compounds, with J.B.S. as a co-inventor. J.I. is a shareholder of ArrowImmune Inc., which is working on immuno-oncology.<br /> (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2666-3791
- Volume :
- 4
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell reports. Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 37992685
- Full Text :
- https://doi.org/10.1016/j.xcrm.2023.101289