Integrin alpha-2 binding agents and use thereof to inhibit cancer cell proliferation

摘要

The invention provides an integrin alpha-2 binding agent and methods of using an integrin alpha-2 binding agent to, e.g., inhibit proliferation of cancer cells, modulate tumor growth in a subject, inhibiting angiogenesis, or treating a fibrotic disorder. The invention further provides a method of producing an antibody, the method comprising propagating cancer cells in a 3-dimensional matrix; immunizing a mammal with the propagated cancer cells; and isolating an antibody from the immunized mammal. A method of identifying an agent that inhibits cancer cell proliferation also is provided.

主权项

1. An anti-integrin alpha-2 antibody or fragment thereof comprising three heavy chain CDRs, CDR-H1, CDR-H2 and CDR-H3 wherein (a) CDR-H1 is SEQ ID NO: 1, CDR-H2 is SEQ ID NO: 2, and CDR-H3 is SEQ ID NO: 3, (b) CDR-H1 is SEQ ID NO: 7, CDR-H2 is SEQ ID NO: 8, and CDR-H3 is SEQ ID NO: 9, or (c) CDR-H1 is SEQ ID NO: 13, CDR-H2 is SEQ ID NO: 14, and CDR-H3 is SEQ ID NO: 15, and three light chain CDRs, CDR-L1, CDR-L2 and CDR-L3 wherein (a) CDR-L1 is SEQ ID NO: 4, CDR-L2 is SEQ ID NO: 5, and CDR-L3 is SEQ ID NO: 6, (b) CDR-L1 is SEQ ID NO: 10, CDR-L2 is SEQ ID NO: 11, and CDR-L3 is SEQ ID NO: 12, or (c) CDR-L1 is SEQ ID NO: 16, CDR-L2 is SEQ ID NO: 17, and CDR-L3 is SEQ ID NO: 18.