Anti-CD147 antibodies, methods and uses
The present invention provides antibodies immunospecific for human CD147 capable of blocking bioactivity of CD147 associated with malignant disease such as the stimulation of MMPs from fibroblast cells by tumor cells, the release of VEGF, and the promotion of angiogenesis. The antibodies of the present invention of are useful in treating malignant disease and those diseases in which CD147 activity is plays a pathogenic role, such as diseases of the eye, lung, and cardiovascular system.
1. An isolated anti-CD147 antibody having Hc-CDR1, Hc-CDR2 and Hc-CDR3 amino acid sequences shown in SEQ ID NO: 10 and Lc-CDR1 Lc-CDR2, and Lc-CDR3 amino acid sequences shown in SEQ ID NO: 9.
2. An isolated anti-CD147 antibody having Hc-CDR1, Hc-CDR2 and Hc-CDR3 amino acid sequences shown in SEQ ID NO: 12 and Lc-CDR1 Lc-CDR2, and Lc-CDR3 amino acid sequences shown in SEQ ID NO: 11.
3. An isolated anti-CD147 antibody having Hc-CDR1, Hc-CDR2 and Hc-CDR3 amino acid sequences shown in SEQ ID NO: 14 and Lc-CDR1 Lc-CDR2, and Lc-CDR3 amino acid sequences shown in SEQ ID NO: 13.
4. An isolated anti-CD147 antibody having Hc-CDR1, Hc-CDR2 and Hc-CDR3 amino acid sequences shown in SEQ ID NO: 16 and Lc-CDR1 Lc-CDR2, and Lc-CDR3 amino acid sequences shown in SEQ ID NO: 15.
5. A humanized antibody comprising a humanized heavy chain and humanized light chain, wherein:
(a) the humanized heavy chain variable region comprises three complementarity determining regions (CDRS) from the mouse 4A5 heavy chain (SEQ ID NO: 12) and a framework from a human acceptor antibody heavy chain; and
(b) the humanized light chain variable region comprises three complementarity determining regions from the mouse 4A5 light chain (SEQ ID NO: 11) and a framework from a human acceptor antibody light chain; and
(c) wherein the humanized antibody specifically binds to a CD147 antigen on the surface of MDA-MB-231 cells.