Abstract 1726: Preclinical evaluation of a novel tumor selectively targeted and activated immunocytokine platform

Abstract

Abstract Interferon alpha (IFNα) is a potent cytokine with receptors expressed universally on virtually all cells types. Recombinant versions of IFNα have demonstrated efficacy in multiple tumor indications and have been FDA approved for treatment of various cancers. However, the full anti-tumor potential of IFNα is not realized with these therapies due to dose limiting toxicity, primarily represented by severe flu-like symptoms resulting from systemic activation of immune cells. Antibody-cytokine fusion proteins have been evaluated as an approach to enhance tumor delivery of the cytokine and thereby increase the therapeutic window. While this approach has merit and can increase the efficacy of such constructs, it typically does not reduce the systemic toxicity since the cytokine is still free to interact with its receptor in circulation. We have designed a novel fusion protein in which the IFNα is active only after it has entered the tumor environment, thereby preventing toxicity resulting from systemic activation of IFNα receptors. Direct antitumor efficacy of an anti-CD138-IFNα2 fusion protein with a tumor selectively cleaved peptide mask was seen in models of multiple myeloma and ovarian cancer. The mask was also shown to prevent IFN mediated activation of peripheral blood cells. Citation Format: Kham R. Trinh, Alex Vasuthaswat, George Ayoub, Sherie L. Morrison, David R. Stover. Preclinical evaluation of a novel tumor selectively targeted and activated immunocytokine platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1726.