CIBLAGE DE CELLULES TUMORALES AVEC DES AGENTS CHIMIOTHÉRAPEUTIQUES CONJUGUÉS À DES ANTICORPS ANTI-MATRIPTASE PAR DES PARTIES DE LIAISON CLIVABLES IN VIVO
The present invention relates to anti-matriptase antibodies and immunoconjugates of anti- 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 an anti-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 an anti-matriptase antibody or immunoconjugates of an anti-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.La présente invention concerne des anticorps anti-matriptase et des immunoconjugués d'anticorps anti-matriptase avec des agents cytotoxiques, ainsi que leur utilisation pour détruire ou inhiber la croissance de cellules cancéreuses exprimant la matriptase, telles que des cellules de myélome multiple et de cancers du sein. En particulier, l'invention concerne des immunoconjugués comprenant un anticorps monoclonal anti-matriptase et des agents anticancéreux tels qu'une auristatine, notamment la monométhyl-auristatine E (MMAE)) et la monométhyl-auristatine F (MMAF), qui ont une activité antitumorale puissante in vivo. De plus, il est important de constater qu'il n'y a pas de perte de poids ou d'autres preuves de toxicité chez les animaux, ce qui indique qu'il n'y a pas de quantité significa
