TNF-IMMUNOCONJUGATES WITH FIBROBLAST ACTIVATION PROTEIN ANTIBODIES AND METHODS AND USES THEREOF

摘要

Protein-immunoco?jugates are provided, particularly TNF conjugates to antibodies and fragments thereof which bind to Fibroblast Activation Protein (FAP). TNF-FAP antibody conjugates are provided wherein the FAP antibody recognizes both human and mouse FAP. These immunoconjugates are useful in the diagnosis and treatment of conditions associated with activated stroma, including wound healing, epithelial cancers, osteoarthritis, rheumatoid arthritis, cirrhosis and pulmonary fibrosis, and more broadly in TNF responsive conditions and disorders, including cancer and hyperproliferative diseases. In addition, the FAP-immunoconjugates can be used for the diagnosis and treatment of FAP positive tumors such as pancreatic cancer, melanoma and sarcomas. The immunoconjugates, antibodies, variable regions or CDR domain sequences thereof, and fragments thereof of the present invention may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof.