Inhibition of solid tumor growth using a new anti-EMMPRIN antibody
EMMPRIN is a new therapeutic target for the treatment of cancer, as its overexpression in many types of tumors is associated with tumor progression, angiogenesis, invasiveness, and metastasis. Previous attempts to knockdown its expression using siRNA succeeded in reducing MMP-9 expression and invasiveness of tumor cells in vitro, confirming the importance of the EMMPRIN protein. Other experiments that raised monoclonal antibodies against the entire extracellular fragment of EMMPRIN showed ambivalent results, suggesting that several different epitopes may be involved in the induction of MMPs, VEGF or additional activities of the protein.
The group of Drs. Rahat, Lahat and Bitterman has developed an epitope-specific polyclonal antibody that inhibited secretion of both VEGF and MMP-9 in vitro from mouse and human tumor cell lines incubated in co-culture with macrophages (presence of macrophages is needed to induce high secretion of pro-angiogenic factors) Furthermore, injection of this antibody in two mice models of subcutaneous tumors significantly delayed cancer progression. Based on the observed cross-reactivity, we now develop a new mouse anti-human EMMPRIN monoclonal antibody based on the human EMMPRIN sequence. A successful antibody with the ability to inhibit the growth of several types of solid tumors could potentially become an adjuvant therapy for a wide range of cancer patients.