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AssigneesRutgers, The State University of New Jersey, Georgetown University
InventorsSiang-Yo Lin, Joseph R. Bertino, Chen-Yong Lin
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The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.
An immunoconjugate comprising an antibody or antigen-binding fragment thereof that binds matriptase in a form selectively expressed on cancer cells, said antibody or fragment covalently linked to a chemotherapeutic agent, wherein said antibody or fragment binds a complex between activated matriptase and its inhibitor HAI-1, wherein said antibody is M69 or an antigen binding fragment thereof, or is a chimeric antibody that comprises the variable regions of M69, or is a humanized antibody that comprises the variable regions of M69.
Dependencies are inferred from the claim text.