Recombinant proteins and their therapeutic uses
A recombinant protein expressing one or more human growth factors, tumor antigens, and/or receptors or epitopes thereof on or within an immunogenic expression creating a recombinant protein in which one or more epitopes are presented on the surface of the sequence in their natural configuration. The growth factor, tumor antigen, and/or receptor, sequence(s) may be expressed within the encoding sequence at appropriate internal positions or at the termini as single expressions or as two or more tandem repeats.
1. A recombinant protein, comprising:
an immunogenic polypeptide;
a peptide spacer selected from the group consisting of SSGGG (SEQ. ID NO: 4), GGSGG (SEQ. ID NO: 3), SSGGGSGG (SEQ. ID NO: 8), SSGGGGSGGG (SEQ. ID NO: 9), TSGGGSG (SEQ. ID NO: 10), TSGGGGSGG (SEQ. ID NO: 11), SSGGGSGGSSG (SEQ. ID NO: 12), GGSGGTSGGGSG (SEQ. ID NO: 13), SGGTSGGGGSGG (SEQ. ID NO: 14), GGSGGTSGGGGSGG (SEQ. ID NO: 15), SSGGGGSGGGSSG (SEQ. ID NO: 16), SSGGGSGGSSGGG (SEQ. ID NO: 17), SSGGGGSGGGSSGGG (SEQ. ID NO: 18), and GGSGGTRPSTAATS (SEQ. ID NO: 19), and
a polypeptide including a neutralizing domain of a self-protein growth factor,
wherein said immunogenic polypeptide is separated from said polypeptide by said peptide spacer.
2. The recombinant protein according to claim 1 , wherein said immunogenic polypeptide includes a cholera toxin B (CT-B) protein.
3. The recombinant protein according to claim 1 , wherein said self-protein growth factor includes an epidermal growth factor (EGF).
4. The recombinant protein according to claim 1 , wherein said neutralizing domain includes a B-loop of an epidermal growth factor (EGF).
5. The recombinant protein according to claim 1 , wherein said self-protein growth factor includes a full length or part thereof of one or more growth factors selected from the group consisting of IGF-1, IGF-2, FGF1, FGF2, TGF-α, TGF-β, VEGF-A, VEGF-B, VEGF-C, VEGF-D, PDGF, NGF, EGF, HGF, BMP's, and IL's 1-6.
6. The recombinant protein according to claim 1 , wherein said polypeptide includes a full length or neutralizing domain of at least two different growth factors.
7. The recombinant protein according claim 1 , wherein said polypeptide includes a full length or neutralizing domain of one or more growth factors as a single domain or as two or more tandem repeats.
8. A process of preparing a multivalent molecule comprising:
assembling multimers from one or more monomeric sub-units to form a synthetic protein including one or more growth factors or parts thereof, wherein the monomeric sub-units are the recombinant protein of claim 1 .
9. The recombinant protein according to claim 1 , wherein said peptide spacer is configured to reduce steric hindrance between said immunogenic polypeptide and said polypeptide.
10. The recombinant protein according to claim 1 , wherein said immunogenic polypeptide includes a cholera toxin B (CT-B) protein.
11. The recombinant protein according to claim 1 , wherein said growth factor is an epidermal growth factor (EGF).
12. An immunogenic composition, comprising:
an immunogenic polypeptide;
a peptide spacer selected from the group consisting of SSGGG (SEQ. ID NO: 4), GGSGG (SEQ. ID NO: 3), SSGGGSGG (SEQ. ID NO: 8), SSGGGGSGGG (SEQ. ID NO: 9), TSGGGSG (SEQ. ID NO: 10), TSGGGGSGG (SEQ. ID NO: 11), SSGGGSGGSSG (SEQ. ID NO: 12), GGSGGTSGGGSG (SEQ. ID NO: 13), SGGTSGGGGSGG (SEQ. ID NO: 14), GGSGGTSGGGGSGG (SEQ. ID NO: 15), SSGGGGSGGGSSG (SEQ. ID NO: 16), SSGGGSGGSSGGG (SEQ. ID NO: 17), SSGGGGSGGGSSGGG (SEQ. ID NO: 18), and GGSGGTRPSTAATS (SEQ. ID NO: 19); and
a polypeptide including a neutralizing domain of a growth factor,
wherein said immunogenic polypeptide is separated from said polypeptide by said peptide spacer.
13. The immunogenic composition of claim 12 , wherein said growth factor is a human self-protein growth factor.
14. The immunogenic composition of claim 12 , wherein said growth factor includes a full length or part thereof of one or more growth factors selected from the group consisting of IGF-1, IGF-2, FGF1, FGF2, TGF-α, TGF-β, VEGF-A, VEGF-B, VEGF-C, VEGF-D, PDGF, NGF, EGF, HGF, BMP's, and IL's 1-6.
15. The immunogenic composition of claim 14 , wherein said growth factor includes a full length or part thereof of IGF-1, IGF-2, EGF, and combinations thereof.