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 the steps of:
attaching ex vivo a dendritic cell asialoglycoprotein receptor (DC-ASGPR)-specific antibody or DC-ASGPR-specific fragment thereof to an antigen to form an antibody-antigen complex, wherein the antigen is an autoantigen; 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 the method occurs in an individual with an autoimmune disorder.
3. The method of claim 2 , wherein the autoimmune disorder is multiple sclerosis.
4. The method of claim 1 , wherein the antigen is myelin basic protein, glutamic acid decarboxylase 65 (GAD 65), native DNA, myelin proteolipid protein, acetylcholine receptor components, thyroglobulin, or the thyroid stimulating hormone (TSH) receptor.
5. The method of claim 1 , wherein the antigen is a fusion protein with the antibody.
6. 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.
7. The method of claim 6 , wherein a complementary cohesin or dockerin domain is attached to the antigen that forms a complex with the antibody.
8. The method of claim 6 , wherein a complementary cohesin or dockerin domain is fused with the antigen.
9. 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.