The present application relates to
cytokine-based bioactivatable drugs and methods of use thereof. The present invention provides a bioactivatable
drug construct platform based on cytokines, aimed at reducing
systemic toxicity, enabling proteins and cytokines, such as IL-15 and IL-2, to have a broader therapeutic use in the treatment of
cancer, autoimmune diseases, inflammatory diseases, viral infections,
transplantation and other disorders. The invention relates to a bioactivator comprising a tissue or
disease site targeting portion D1 domain, a bioactivatable portion D2 domain and a shielding portion D3 domain. The active
moiety of VitoKine remains
inert until it is locally activated by an upregulated
protease in diseased tissue, which limits binding of the active
moiety to receptors or targets in the periphery or on the
cell surface of non-diseased cells and tissues, prevents pathway over-activation and reduces undesirable "
extracorporeal" "in-target"
toxicity. Prior to
protease activation, the inertness of the VitoKine active
moiety significantly reduces potential
antigen or target silencing, extends
in vivo half-life and improves
biodistribution,
bioavailability and therapeutic
efficacy.