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 sequence including cholera toxin B subunit (CT-B) or E. coli heat-labile LT B subunit (LT-B);
a peptide spacer configured to reduce steric hindrance; and
a polypeptide sequence comprising amino acids 11 to 36 of SEQ ID NO: 38;
wherein said polypeptide sequence is separated from said immunogenic polypeptide sequence by said peptide spacer within the recombinant protein.
2. The recombinant protein according to claim 1 , wherein the peptide spacer is selected from the group consisting of 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).
3. The recombinant protein according to claim 1 , wherein the immunogenic polypeptide sequence further comprises a sequence comprising at least a portion of a tumor antigen.
4. The recombinant protein according to claim 1 , wherein the immunogenic polypeptide sequence further comprises a sequence comprising at least a portion of a receptor.
5. The recombinant protein according to claim 1 , wherein the immunogenic polypeptide sequence further comprises a sequence comprising at least a portion of a tumor antigen and a sequence comprising at least a portion of a receptor.
6. The recombinant protein according to claim 1 , comprising a full length or a portion of at least two different growth factors.
7. The recombinant protein according to claim 1 , comprising a full length or a portion of one or more growth factors in said protein as a single domain or as two or more tandem repeats.
8. The recombinant protein according to claim 6 , comprising a full length or a portion of one or more of the following growth factors: IGF-1, IGF-2, FGF1, FGF2, TGF-∝, TGF-β, VEGF-A, VEGF-B, VEGF-C, VEGF-D, PDGF, NGF, EGF, HGF, BMP's, and IL's 1-6.
9. The recombinant protein according to claim 3 , wherein said at least a portion of said tumor antigen includes a full length or a portion of two to four different tumor antigens, or a full length or a portion of one or more tumor antigens present as single epitopes or as two or more tandem repeats.
10. The recombinant protein of claim 5 , wherein said at least a portion of said receptor includes a full length or part thereof of Human Epidermal growth factor Receptor 2 (Her 2) or Human Epidermal growth factor Receptor 3 (Her 3).
11. The recombinant protein of claim 5 wherein said full length or portion of said receptor includes a full length or portion of two to four different receptors, or a full length or portion of one or more receptors as single epitopes or as two or more tandem repeats.
12. A process of preparing a multivalent molecule comprising:
assembling multimers from one or more recombinant proteins according to claim 1 .