Engineered antibody-interferon mutant fusion molecules

摘要

The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to fusion molecule constructs wherein a tumor associated antigen (TAA) antibody (Ab) serves as a targeting moiety to selectively deliver a cytokine to a tumor cell for purposes of killing or inhibiting the growth or proliferation of said tumor cell. In various embodiments, the engineered fusion molecules comprise a TAA Ab fused to an interferon-alpha (IFN-α) mutant molecule. The engineered Ab-IFN-α mutant fusion molecules of the present invention demonstrate improved therapeutic index and preserved or increased efficacy as compared to Ab-wildtype IFN-α fusion molecules, and/or demonstrate improved PK properties as compared to Ab-wildtype IFN-α fusion molecules.

主权项

1. A genetically engineered fusion molecule comprising a tumor-associated antigen (TAA) antibody (Ab) attached to an interferon alpha (IFN-α) mutant molecule, wherein said antibody is attached directly to said IFN-α mutant molecule, wherein said IFN-α mutant molecule is a mutated human IFN-α2 molecule comprising at least one mutation in SEQ ID NO: 13, wherein said mutation is selected from H57A, E58A, L30A, and F27A, and wherein the TAA antibody is an IgG antibody.