| abstract |
The present disclosure reduces systemic mechanism-based toxicity and provides broader treatments for proteins and cytokines such as IL-15 and IL-2 for the treatment of cancer, autoimmune diseases, inflammatory diseases, viral infections, transplants and various other disorders. It provides a cytokine-based bioactivating drug construct ("VitoKine") platform that aims to bring about useful utility. The novel VitoKine constructs of the present invention include: 1) tissue or disease site targeting moiety D1 domain (“D1”), 2) bioactivating moiety D2 domain (“D2”), and hiding moiety D3 Domain ("D3"). Importantly, because VitoKine constructs can remain inactive until they are locally activated by proteases that are upregulated in diseased tissues, this is not at the periphery of diseased cells and tissues or on receptors or targets on the cell-surface. Restricting the binding of the active moiety to it will prevent overactivation of the pathway and reduce undesirable “in-target” “off tissue” toxicity. Additionally, the protease activated before the inert of VitoKine active moiety will be significantly reducing the potential antigen or target sink, thus causing the in vivo distribution of extending the in vivo half-life and improve, the bioavailability and therapeutic efficacy . |