The present disclosure provides a cytokine-based bioactivatable drug construct ("VitoKine") platform that aims to reduce systemic mechanism-based toxicities and lead to broader therapeutic utility for proteins and cytokines such as IL-15 and IL-2 for the treatment of cancer, autoimmune diseases, inflammatory diseases, viral infection, transplantation and various other disorders. The novel VitoKine constructs of the present invention comprise: 1) a tissue or disease site targeting moiety D1 domain ("D1"), 2) a bioactivatable moiety D2 domain ("D2"), and a concealing moiety D3 domain ("D3"). Importantly, because the "active moiety" of the VitoKine construct will remain inert until activated locally by proteases that are upregulated in diseased tissues, this will limit binding of the active moiety to the receptors or to the targets in the peripheral or on the cell-surface of non-diseased cells and tissue to prevent over-activation of the pathway and reduce undesirable "on-target" "off tissue" toxicities. Additionally, the inertness of the VitoKine active moiety prior to protease activation will significantly decrease the potential antigen or target sink, and thus, prolong the in vivo half-life and result in improved biodistribution, bioavailability and therapeutic efficacy.La présente invention concerne une plateforme de construction d'un médicament bioactivable à base de cytokine (" VitoKine ") qui vise à réduire les toxicités liées à un mécanisme systémique et conduit à une utilité thérapeutique plus large pour les protéines et cytokines telles que IL-15 et IL-2 pour le traitement du cancer, de maladies auto-immunes, de maladies inflammatoires, d'une infection virale, d'une transplantation et de divers autres troubles. Les nouvelles constructions de VitoKine selon la présente invention comprennent : 1) un domaine D1 de fraction ciblant un tissu ou un site de maladie ("D1"), 2) un domaine D2 de fraction bioactivable ("D2"), et un domaine D3 de fraction de dissimulatio
