The present invention relates generally to novel
protease activatable
interleukin-2 (IL-2) polypeptides and immunoconjugates comprising (i) an IL-2 polypeptide, (ii) a masking
moiety and (iii) a
linker comprising a first
protease cleavage site wherein the
linker has a length of 20 to 45 amino acids wherein the masking
moiety is covalently linked to the IL-2 polypeptide through the
linker, wherein the masking
moiety is capable of binding to the IL-2 polypeptide, thereby reversibly concealing the IL-2 polypeptide, where the masking moiety comprises a second
protease cleavage site, where the masking moiety does not conceal the IL-2 polypeptide when cleavage is at the first protease cleavage site and / or the second protease cleavage site. The present invention also relates to polynucleotides encoding such protease activatable
interleukin-2 (IL-2) polypeptides and immunoconjugates, as well as vectors and host cells comprising such polynucleotides. The invention also relates to methods for producing the protease activatable
interleukin-2 (IL-2) polypeptides and immunoconjugates of the invention, and methods of using these protease activatable interleukin-2 (IL-2) polypeptides and immunoconjugates in the treatment of
disease.