engineered interferon alpha-2b prodrug JZP898

An engineered, prodrug form of the human cytokine interferon alpha-2b (IFN-alpha-2b), composed of IFN-alpha-2b linked to a high affinity blockade element via a tumor protease-sensitive linker, and a half-life extension domain, with potential immunomodulatory and antineoplastic activities. Upon administration of engineered IFN-alpha-2b prodrug JZP898, IFN-alpha-2b is bound to the blockade element and pharmacologically inactive. Upon proteolytic cleavage in the tumor microenvironment (TME), active IFN-alpha-2b is released. IFN-alpha-2b binds to specific IFN cell-surface receptors. This activates IFN-mediated signal transduction pathways and induces the transcription and translation of genes with interferon-stimulated response elements (ISREs); the protein products mediate immunomodulating and antiproliferative effects. The selective activation in the TME enhances the IFN-alpha-2b-mediated immune responses against tumor cells while sparing the unwanted effects of systemic, peripheral immune activation. The inclusion of the half-life extension domain prolongs the agent's exposure in the tumor.