Methods of cancer treatment with PD-L1 targeted interferon therapeutic agents

A method for treating cancer, comprising administering to a subject in need thereof an effective amount of a chimeric protein comprising:

• (a) a targeting moiety that comprises a recognition domain that recognizes and binds to programmed cell death protein 1 ligand 1 (PD-L1), wherein the targeting moiety comprises a recombinant heavy-chain-only antibody (VHH), a single-chain antibody (scFv), or a shark heavy-chain-only antibody (VNAR);
• and
• (b) a modified signaling agent, wherein the modified signaling agent is a human interferon alpha 2 (IFNα2) comprising an amino acid sequence having at least 98% identity with a sequence selected from SEQ ID NO:
• 179 or 180 and having one or more mutations at one or more position of amino acids 144-154,
• wherein the mutated human IFNα2 has reduced affinity or activity as compared to wild type human IFNα2, and the reduced affinity or activity of the mutated human IFNα2 is restorable by the targeting moiety,
• wherein the cancer comprises cells expressing PD-L1.