Therapeutic interferon alpha 1 proteins

A chimeric protein complex comprising:

• (a) a human interferon alpha 1 (IFNα1) comprising an amino acid sequence having at least 97% identity with SEQ ID NO:
• 1 and having a substitution or deletion at position C86,
• (b) one or more targeting moieties, the targeting moieties comprising single-domain antibodies or scFvs which specifically bind to a cellular target;
• wherein:
• the IFNα1 of the chimeric protein complex exhibits attenuated activity as compared to wild type IFNα1 having SEQ ID NO:
• 1;
• and
• the IFNα1 of the chimeric protein complex exhibits activity which is induced by attachment to the one or more targeting moieties and is greater than that of wild type IFNα1 having SEQ ID NO:
• 1, and
• (c) an Fc domain connecting the IFNα1 and the one or more targeting moieties, the Fc domain having one or more mutations that reduce or eliminate one or more effector functions of the Fc domain, promotes Fc chain pairing in the Fc domain, or stabilizes a hinge region in the Fc domain, and being derived from a human IgG, selected from human IgG1, IgG2, IgG3, and IgG4,
• wherein the chimeric protein complex is a heterodimer having a trans orientation/configuration, as relates to any targeting moiety and IFNα1, relative to each other, or any targeting moieties relative to each other, or any IFNα1s relative to each other.