Modified antibody
Recombinant antibody-based molecules that trigger both T-cell and B-cell immune responses are disclosed. The recombinant molecules are comprised by at least one targeting unit and at least one antigenic unit connected through a dimerization motif. Also disclosed are nucleic acid molecules encoding the recombinant antibody-based molecule and methods of treating multiple myeloma or lymphoma in a patient using the recombinant antibody-based molecules or the nucleic acid molecules.
1. A method for inducing an immune response against an antigen in an animal, including a human being, the method comprising administering to the animal, an effective amount of at least one nucleic acid which encodes a monomer unit of a dimeric recombinant antibody-based molecule, which comprises two such monomer units that are connected through a dimerization motif, wherein said dimerization motif
consists of a hinge region and a carboxyterminal C domain and comprises a hinge region and a Cγ3 domain of each monomer unit, wherein each hinge region contributes to dimerization via disulfide bridging to the other hinge region and each Cγ3 domain contributes to dimerization via hydrophobic interactions to the other Cγ3 domain,
and wherein said monomer units each comprises
an antigenic unit derived from said antigen, and
a targeting unit for an antigen presenting cell,
and wherein said monomer units both lack a CH2 domain,
whereby administration of said nucleic acid induces production of said recombinant dimeric antibody-based molecule in said animal whereby an immune response is induced against said antigen.
2. The method of claim 1 , wherein administering the nucleic acid comprises delivering the nucleic acid by electroporation.
3. The method of claim 1 , wherein said targeting unit(s) is/are a single chain fragment variable of Ig (scFv).
4. The method of claim 3 , wherein said scFv is anti-HLA, anti-CD14, anti-CD40, or anti-toll-like receptor.
5. The method of claim 4 , wherein said anti-HLA is anti-HLA-DP.
6. The method of claim 4 , wherein said anti-toll-like receptor is anti-toll-like receptor 2.
7. The method of claim 1 , wherein at least one targeting unit is a ligand.
8. The method of claim 7 , wherein said ligand is soluble CD40 ligand or a chemokine.
9. The method of claim 7 , wherein said ligand is a chemokine.
10. The method of claim 9 , wherein said chemokine is RANTES or MIP-1α.
11. The method of claim 9 , wherein said chemokine is MIP-1α.
12. The method of claim 1 , wherein at least one targeting unit is a bacterial antigen.
13. The method of claim 12 , wherein the bacterial antigen is a flaggelin.
14. The method of claim 1 , wherein the targeting units have the ability to target antigen presenting cells (APC).
15. The method of claim 1 , wherein the targeting units have the ability to target HLA, CD14, CD40, toll-like receptors, or a chemokine receptors.
16. The method of claim 15 , wherein said HLA is HLA-DP.
17. The method of claim 1 , wherein the targeting units have the ability to target chemokine receptors.
18. The method of claim 1 , wherein the antigenic unit(s) is/are an antigenic scFv.
19. The method of claim 18 , wherein the antigenic scFv is derived from a monoclonal Ig produced by myeloma or lymphoma.
20. The method of claim 18 , wherein the antigenic unit(s) is/are a telomerase, or a functional part thereof.
21. The method of claim 20 , wherein said telomerase is hTERT.
22. The method of claim 1 , wherein the antigenic unit(s) is/are derived from a bacterium.
23. The method of claim 22 , wherein the bacterium derived antigenic unit(s) is/are a tuberculosis antigen.
24. The method of claim 1 , wherein the antigenic unit(s) is/are derived from a virus.
25. The method of claim 24 , wherein the virus derived antigenic unit(s) is/are derived from HIV.
26. The method of claim 25 , wherein the HIV derived antigenic unit(s) is/are derived from gp120.
27. The method of claim 1 , wherein the carboxyterminal C domain is derived from IgG.
28. The method of claim 1 , wherein the dimerization motif has the ability to homodimerize.
29. The method of claim 1 , comprising administering a vector comprising the nucleic acid.