Soluble Universal ADCC-Enhancing Synthetic Fusion Gene and Peptide Technology and Its Use Thereof

Abstract

Novel synthetic biology-based ADCC technologies are provided that enhance or enable ADCC responses, for example, through a rationally-designed soluble universal ADCC enhancer protein (SUAEP) where a high-affinity CD3-binding domain is fused to a high-affinity Fc-binding domain. The SUAEP technology can be used to prevent or treat cancers, infectious, inflammatory or autoimmune diseases, and other diseases where elimination of diseased cells is desirable.

1 - 12 . (canceled) 
     
     
         13 . A method of treating a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising a fusion protein, wherein said fusion protein comprises a binding domain for an antibody's Fc fragment (“Fc-binding domain”), and a binding domain for CD3 (“CD3-binding domain”), wherein said Fc-binding domain comprises the ectodomain of CD64, and wherein said CD3-binding domain comprises an scFv comprising the variable light (VL) and variable heavy (VH) chains of an anti-CD3 monoclonal antibody. 
     
     
         14 . The method of  claim 13 , wherein said pharmaceutical composition further comprises a pharmaceutically acceptable excipient. 
     
     
         15 . The method of  claim 13 , wherein said anti-CD3 monoclonal antibody is an OKT3 monoclonal antibody. 
     
     
         16 . The method of  claim 15 , wherein said anti-CD3 monoclonal antibody is a dhOKT3 (deimmunized, humanized OKT3). 
     
     
         17 . The method of  claim 13 , wherein said anti-CD3 monoclonal antibody is a humanized TR66. 
     
     
         18 . The method of  claim 13 , wherein said ectodomain of CD64 is fused with said scFv of anti-CD3 monoclonal antibody through a flexible serine-glycine linker consisting of multiple units of serine residues and glycine residues. 
     
     
         19 . The method of  claim 13 , wherein the amino acid sequence of said ectodomain of CD64 is SEQ ID NO:1. 
     
     
         20 . The method of  claim 13 , wherein said fusion protein comprises the amino acid sequence of SEQ ID NO:3. 
     
     
         21 . The method of  claim 18 , wherein the amino acid sequence of said flexible serine-glycine linker and said scFv of anti-CD3 monoclonal antibody is SEQ ID NO:2. 
     
     
         22 . The method of  claim 13 , further comprising administering a therapeutic antibody against at least one cell-surface antigen. 
     
     
         23 . The method of  claim 22 , wherein said therapeutic antibody is selected from the group consisting of antibodies that are anti-PD-1, anti-PD-L1, anti-CTLA4, anti-CD19 and anti-CD20 antibodies, respectively. 
     
     
         24 . The method of  claim 22 , wherein said therapeutic antibody comprises an Fc region similar to the human IgG4. 
     
     
         25 . The method of  claim 13 , wherein said method is used for treating a condition that is selected from the group consisting of a cancer, an inflammatory disease, an autoimmune disease, a transplant rejection and an infection. 
     
     
         26 . The method of  claim 13 , wherein said method is used for treating cancer. 
     
     
         27 . The method of  claim 22 , wherein said therapeutic antibody is selected from the group consisting of Rituxan, Herceptin, and Trastuzumab. 
     
     
         28 . The method of  claim 24 , wherein said therapeutic antibody is Nivolumab.