Molecular conjugates comprising human monoclonal antibodies to dendritic cells

Abstract

Isolated human monoclonal antibodies and antigen-binding portions thereof which specifically bind to dendritic cells are disclosed. Also disclosed are bispecifics, immunotoxins and antigen conjugates which include the antibodies or antibody portions. The human antibodies can be produced in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

1 - 3 . (canceled) 
     
     
         4 . A molecular conjugate comprising a monoclonal antibody, or antigen binding portion thereof, that binds to human dendritic cells linked to an antigen, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         5 . A molecular conjugate comprising a monoclonal antibody, or antigen binding portion thereof, that binds to human dendritic cells linked to an antigen, wherein the antibody comprises a heavy chain variable region encoded by the nucleotide sequence of SEQ ID NO: 3 or a light chain variable region encoded by the amino acid sequence of SEQ ID NO: 1. 
     
     
         6 . The molecular conjugate of  claim 4  or  5  wherein the antibody, or antigen binding portion thereof, binds to the human macrophage mannose receptor. 
     
     
         7 . The molecular conjugate of  claim 4  wherein the antigen is a melanoma associated antigen selected from the group consisting of MART1, melan-A, NY-ESO-1, MAGE-1, MAGE-3, high molecular weight-melanoma associated antigen (HMW-MAA), Gp100 and Pmel-17. 
     
     
         8 . The molecular conjugate of  claim 4  wherein the antigen is selected from the group consisting of a component of a pathogen, a tumor antigen, and an autoantigen. 
     
     
         9 . A molecular conjugate comprising a monoclonal antibody, or antigen binding portion thereof, that binds to the human macrophage mannose receptor on dendritic cells linked to an antigen, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2, linked to Pmel-17 antigen. 
     
     
         10 . A molecular conjugate comprising a monoclonal antibody, or antigen binding portion thereof, that binds to the human macrophage mannose receptor on dendritic cells linked to an antigen, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2, linked to NY-ESO-1 antigen. 
     
     
         11 . A composition comprising a molecular conjugate of  claim 4  and a pharmaceutically acceptable carrier. 
     
     
         12 . The composition of  claim 11  further comprising an adjuvant. 
     
     
         13 . The molecular conjugate of  claim 4  produced as a recombinant fusion protein or a chemical conjugate.