Agents that engage antigen-presenting cells through dendritic cell asialoglycoprotein receptor (DC-ASGPR)
The present invention includes compositions and methods for making and using anti DC-ASGPR antibodies that can, e.g., activate DCs and other cells.
1. A method for increasing the effectiveness of antigen presentation by dendritic cells in an individual comprising:
attaching ex vivo a DC-ASGPR-specific antibody or DC-ASGPR-specific fragment thereof to an antigen to form an antibody-antigen complex; and
delivering an effective amount of the complex to the individual, wherein the antigen is processed and presented by a dendritic cell that has been contacted with the antibody-antigen complex, wherein the antibody or fragment thereof comprises an immunoglobulin heavy chain selected from the group consisting of SEQ ID NO: 5, 7, 9, or 11, wherein the antibody or fragment thereof targets a human DC-ASGPR.
2. The method of claim 1 , wherein increased effectiveness of the dendritic cells is determined using allogeneic CD8+ T cells.
3. The method of claim 1 , wherein the antigen is a fusion protein with the antibody.
4. The method of claim 1 , wherein the antigen comprises a bacterial, viral, fungal, protozoan or cancer protein.
5. The method of claim 1 , wherein the antibody is attached to a cohesin or a dockerin domain capable of forming a cohesin/dockerin binding pair.
6. The method of claim 5 , wherein a complementary cohesin or dockerin domain is attached to the antigen that forms a complex with the antibody.
7. The method of claim 5 , wherein a complementary cohesin or dockerin domain is fused with the antigen.
8. The method of claim 1 , wherein the antibody or fragment thereof comprises an immunoglobulin light chain selected from the group consisting of SEQ ID NO:6, 8, 10, or 12.
9. A method for increasing the effectiveness of dendritic cells comprising:
isolating dendritic cells from an individual;
exposing the dendritic cells to an effective amount of a complex of an antigen and a DC-ASGPR-specific antibody or DC-ASGPR-specific fragment thereof, wherein the antibody or fragment thereof comprises an immunoglobulin heavy chain selected from the group consisting of SEQ ID NO: 5, 7, 9, or 11, and wherein the antibody or fragment thereof targets a human DC-ASGPR; and
reintroducing the cells into the individual.