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 doxorubicin (DOX) are introduced which are equipotent to anticancer agents used in free form but exhibit significantly reduced cardiotoxicity and almost no adverse effects on normal bone marrow-derived mesenchymal stromal cells that do not express matriptase. 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.

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