| Mechanism of Action | TRC093 (MT293) is a recombinant humanized IgG1 monoclonal antibody that inhibits angiogenesis, tumor cell growth and metastasis by binding cleaved collagen, which is predominantly produced in the extracellular matrix of tumors. TRC093 targets collagen found in the basement membrane of tumor blood vessels. Collagen is a essential triple helix of polypeptide chains found in the extracellular matrix which is involved with many cellular processs including cell proliferation, adhesion, migration, and angiogenesis (neovascularization - growth of new blood vessels). Matrix metalloproteinase enzymes (MMPs) remodel and denature collagen during angiogenesis, causing changes in bioactive sites which results in altered proliferation, adhesion and migration of cells. TRC093 specifically binds to mice breast cancer blood vessel tumors, inhibiting tumor growth. It is proposed that TRC093 binds to hydroxyproline residues of GPO sequences (the major platelet-activating motif within collagen and essential for collagen folding) when they are exposed by thermal denaturation or partially proteolytically degraded by MMPs. TRC093 may target many different types of cancer as a critical component of the TRC093 epitope is a GPOG sequence which are present in high numbers in many different types of collagen. |