Oncotarget

Research Papers:

Targeting an engineered cytokine with interleukin-2 and interleukin-15 activity to the neovasculature of solid tumors

Michael R. Mortensen _, Jacqueline Mock, Marco Bertolini, Marco Stringhini, Marco Catalano and Dario Neri

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Oncotarget. 2020; 11:3972-3983. https://doi.org/10.18632/oncotarget.27772

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Abstract

Michael R. Mortensen1, Jacqueline Mock1, Marco Bertolini1, Marco Stringhini1, Marco Catalano1 and Dario Neri1

1 Department of Chemistry and Applied Biosciences (D-CHAB), Institute for Pharmaceutical Sciences (IPW), 8093 Zurich, Switzerland

Correspondence to:

Michael R. Mortensen,email: michael.mortensen@pharma.ethz.ch

Keywords: immunotherapy; immunocytokines; EDB of fibronectin; antibody-cytokine fusion proteins; engineered cytokine

Received: July 30, 2020     Accepted: September 24, 2020     Published: November 03, 2020

Copyright: © 2020 Mortensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

There is a growing interest in the antibody-based delivery of cytokines to the tumor environment as a means to boost the anti-cancer activity of tumor-resident T cells and NK cells. Here, we describe the expression and characterization of fusion proteins, featuring the L19 antibody (specific to the alternatively-spliced EDB domain of fibronectin) and an engineered cytokine with interleukin-2 and interleukin-15 properties. The cytokine moiety was fused either at the N-terminal or at the C-terminal extremity and both fusion proteins showed a selective tumor accumulation in a quantitative biodistribution experiment. The N-terminal fusion inhibited tumor growth in immunocompetent mice bearing F9 carcinomas or WEHI-164 sarcomas when used as single agent. The anticancer activity was compared to the one of the same cytokine payload used as recombinant protein or fused to an anti-hen egg lysozyme antibody, serving as negative control of irrelevant specificity in the mouse. These results indicate that the antibody-based delivery of engineered cytokines to the tumor neovasculature may mediate a potent anticancer activity.


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