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 recombinant antibody-based dimeric molecule, wherein said antibody-based dimeric molecule comprises two monomer units connected through a dimerization motif, said dimerization motif comprising an Ig hinge region and a Cγ3 domain of each monomer unit, wherein each Ig hinge region contributes to dimerization via disulfide bridging to the other Ig hinge region and each Cγ3 domain contributes to dimerization via hydrophobic interactions to the other Cγ3 domain, and wherein each of said monomer units comprises a targeting unit for an antigen presenting cell and an antigenic unit, wherein said targeting unit and said antigenic unit in the monomer unit are separated by said dimerization motif and wherein said monomer units each lack a CH2 domain.
2. The recombinant molecule of claim 1 , wherein at least one of said targeting units is a single chain fragment variable of Ig (scFv).
3. The recombinant molecule of claim 2 , wherein said scFv is anti-HLA, anti-CD14, anti-CD40, or anti-toll-like receptor.
4. The recombinant molecule of claim 1 , wherein at least one of said targeting units is a ligand.
5. The recombinant molecule of claim 4 , wherein said ligand is soluble CD40 ligand or a chemokine.
6. The recombinant molecule of claim 5 , wherein said ligand is a chemokine.
7. The recombinant molecule of claim 6 , wherein said chemokine is RANTES or Macrophage Inflammatory Protein 1 alpha (MIP-1alpha).
8. The recombinant molecule of claim 7 , wherein said chemokine is MIP-1alpha.
9. The recombinant molecule of claim 1 , wherein at least one of said targeting units is a bacterial antigen.
10. The recombinant molecule of claim 1 , wherein said targeting units have the ability to target CD14, CD40, a toll-like receptor, HLA or HLA-DP.
11. The recombinant molecule of claim 1 , wherein said targeting units have the ability to target a chemokine receptor.
12. The recombinant molecule of claim 1 , wherein at least one of said antigenic units is an antigenic scFv.
13. The recombinant molecule of claim 12 , wherein said antigenic scFv has VL and VH chains from a monoclonal Ig produced by myeloma or lymphoma.
14. The recombinant molecule of claim 1 , wherein at least one of said antigenic units is a telomerase or a functional part thereof.
15. The recombinant molecule of claim 1 , wherein at least one of said antigenic units is derived from an infectious agent.
16. The recombinant molecule of claim 1 , wherein at least one of said antigenic units is derived from a bacterium.
17. The recombinant molecule of claim 1 , wherein at least one of said antigenic units is derived from a virus.
18. The recombinant molecule of claim 17 , wherein said virus-derived antigenic unit is derived from HIV.
19. A composition comprising the recombinant molecule according to claim 1 in combination with a physiologically acceptable diluent or carrier.
20. 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 the recombinant molecule of according to claim 1 .