Composition and method for modulating dendritic cell-t cell interaction
The present invention relates to the use of a compound that binds to a C-type lectin on the surface of a dendritic cell, in the preparation of a composition for modulating, in particular reducing, the immune response in an animal, in particular a human or another mammal. The composition in particular modulates the interactions between a dendritic cell and a T-cell, more specifically between a C-type lectin on the surface of a dendritic cell and an ICAM receptor on the surface of a T-cell. The compositions can be used for preventing/inhibiting immune responses to specific antigens, for inducing tolerance, for immunotherapy, for immunosuppression, for the treatment of autoimmune diseases, and the treatment of allergy. The compound that binds to a C-type lectin is preferably chosen from mannose, fucose, plant lectins, antibiotics, sugars, proteins or antibodies against C-type lectins. The invention also relates to such antibodies.
1. A conjugate molecule comprising: an antigen attached to an antibody, or an antigen binding fragment of an antibody, that binds to a protein with the amino acid sequence of SEQ ID NO: 2 (DC-SIGN) on the surface of a dendritic cell.
2. The conjugate molecule of claim 1 , wherein said antibody is a monoclonal antibody.
3. The conjugate molecule of claim 1 , wherein said antigen binding fragment is a F(ab) 2 , Fab′, Fab, or Fv fragment.
4. The conjugate molecule of claim 2 , wherein said antibody is selected from the group consisting of: i) an antibody produced by hybridoma ECACC accession number 99040818 and ii) an antibody produced by hybridoma ECACC accession number 99040819.
5. The conjugate molecule of claim 1 , wherein said antigen is attached to said antibody, or an antigen binding fragment of said antibody, by a) covalent binding, b) ligand-ligand interaction, c) complexing, d) ligation, or e) expression of a fusion protein comprising said antigen and said compound.
6. The conjugate molecule of claim 1 , wherein the antigen is a cancer antigen.
7. The conjugate molecule of claim 6 , wherein the cancer antigen is selected from the group consisting of gp 100, g250, p53, MAGE, BAGE, GAGE, MART 1, Tyrosinase related protein II, and Tyrosinase related protein.
8. The conjugate molecule of claim 1 , wherein the antigen is an antigen from an infectious micro-organism.
9. The conjugate molecule of claim 8 , wherein the micro-organism causes influenza, mumps, measles, rubella, diphtheria, or tetanus.
10. The conjugate molecule of claim 8 , wherein the antigen is selected from the group consisting of Haemophilus influenzae, Neisseria, Bordetella pertussis, Polyomyletus, Pneumococcus, HIV, and Herpes Simplex virus.
11. A pharmaceutical composition comprising the conjugate molecule of claim 1 .
12. A composition comprising the conjugate molecule of claim 1 and at least one pharmaceutically acceptable carrier, excipient, adjuvant or formulant.