Phage-peptide constructs for stimulation of an anti-cancer immune response against cd47

Abstract

Disclosed are recombinant bacteriophage constructs and related exogenous peptide sequences for generating immune responses against CD47. The disclosed recombinant phage constructs bind to antibodies against CD47 and can be administered to an animal to generate an immune response against CD47, including generating anti-CD47 antibodies. The disclosed recombinant phage may comprise an amino acid sequence of CD47, epitopic fragments, variants, or functional mimics thereof. Also disclosed are methods for making and selecting such recombinant phage constructs and compositions that comprise such constructs (e.g., compositions for inducing an immune response against CD47 including pharmaceutical or veterinary compositions used as vaccines). Also disclosed are recombinant polynucleotides comprising genomic nucleic acid of the recombinant phage constructs disclosed herein.

1 - 7 . (canceled) 
     
     
         8 . A homogenous population of recombinant bacteriophage comprising an exogenous amino acid sequence that binds to an anti-CD47 antibody. 
     
     
         9 . The homogenous population of recombinant bacteriophage of  claim 8 , wherein the exogenous amino acid sequence is selected from: GLSDYYRALAN (SEQ ID NO:1), GITEYLRTINIG (SEQ ID NO: 2), DYSLRLQYGHTY (SEQ ID NO:3), GLTDYLG (SEQ ID NO:4), EYVAPFNFLEWK (SEQ ID NO:5), YSDTSLSYMQRY (SEQ ID NO:6), AND GLGDRLSHGHTI (SEQ ID NO:7). 
     
     
         10 . The homogenous population of recombinant bacteriophage of  claim 8 , wherein the exogenous amino acid sequence is fused with the gpIII protein of the bacteriophage or the exogenous amino acid sequence is inserted in the gpIII protein of the bacteriophage. 
     
     
         11 . The homogenous population of recombinant bacteriophage of  claim 8 , wherein the exogenous amino acid sequence is fused with the gpVIII protein of the bacteriophage or the exogenous amino acid sequence is inserted in the gpVIII protein of the bacteriophage. 
     
     
         12 - 15 . (canceled) 
     
     
         16 . An immunogenic composition comprising:
 (a) the homogenous population of recombinant bacteriophage of  claim 8 ; and   (b) a suitable excipient, carrier, or diluent.   
     
     
         17 . The composition of  claim 16 , further comprising an adjuvant. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . A method for producing an immune response against CD47 in a subject in need thereof, the method comprising administering the immunogenic composition of  claim 16  to the subject. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . A method for treating a subject having a cancer that expresses CD47, the method comprising administering an effective amount of the composition of  claim 16  to the subject for treating the cancer. 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . A method for selecting peptides that bind to an anti-CD47 antibody, the method comprising:
 (a) contacting a recombinant bacteriophage library with the anti-CD47 antibody; and   (b) selecting bacteriophage from the library that bind specifically to the anti-CD47 antibody.   
     
     
         27 . The method of  claim 26 , comprising first contacting the bacteriophage library with a control antibody which is not the anti-CD47 antibody and removing the bacteriophage that bind to the control antibody. 
     
     
         28 . An immunogenic composition for inducing an immune response against cancer cells comprising a peptide-based antigen mimic and a peptide carrier wherein the peptide-based antigen mimic induces an immune response against CD47. 
     
     
         29 . The immunogenic composition of  claim 28 , wherein the peptide-based antigen mimic is linked to a peptide carrier. 
     
     
         30 . The immunogenic composition of  claim 29 , wherein the peptide carrier is a protein, virus, bacteriophage, microscopic particle, compound, or an expression vector that encodes the peptide-based antigen mimic. 
     
     
         31 . The immunogenic composition of  claim 30 , wherein the peptide-based antigen mimic is selected from at least one of the following peptides: SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO: 7. 
     
     
         32 . A method for generating homogenous population of recombinant bacteriophage of  claim 8 , the method comprising:
 a) contacting a recombinant bacteriophage library with the anti-CD47 antibody; and   (b) selecting bacteriophage from the library that bind specifically to the anti-CD47 antibody.   
     
     
         33 . The method of  claim 32 , comprising first contacting the bacteriophage library with a control antibody which is not the anti-CD47 antibody and removing the bacteriophage that bind to the control antibody.