Masked cytokines and methods of use thereof

A prodrug comprising a cytokine moiety, a masking moiety, and a carrier moiety, wherein:

• a) the masking moiety binds to the cytokine moiety and inhibits a biological activity of the cytokine, wherein the masking moiety comprises a single chain variable fragment (scFv) against the cytokine moiety or comprises an extracellular domain (ECD) of a receptor for the cytokine moiety;
• b) the carrier moiety comprises an antigen-binding moiety, wherein the antigen-binding moiety binds to an antigen expressed on the surface of a target immune cell;
• and
• c) the masking moiety is linked directly or indirectly to the carrier moiety;
• wherein the target immune cell expresses on its surface a cytokine receptor for the cytokine moiety such that when the prodrug binds to the antigen on the target immune cell through the antigen-binding moiety, the cytokine moiety binds to the cytokine receptor on the target immune cell and exerts the biological activity on the target immune cell,
• wherein the cytokine moiety comprises an IL-2 polypeptide, an IL-7 polypeptide, or an IL-21 polypeptide.