Anti-mesothelin antibodies
This invention relates to the use of monoclonal and polyclonal antibodies that specifically bind to and become internalized by mesothelin-positive cells and also induce an immune effector activity such as antibody dependent cellular cytotoxicity. The antibodies are useful in specific delivery of pharmacologic agents to mesothelin expressing cells as well as eliciting an immune-effector activity particularly on tumor cells and precursors. The invention is also related to cells expressing the monoclonal antibodies, polyclonal antibodies, antibody derivatives, such as human, humanized, and chimeric monoclonal antibodies, antibody fragments, mammalian cells expressing the monoclonal antibodies, derivatives and fragments, and methods of treating cancer using the antibodies, derivatives and fragments.
1. A method of inhibiting the growth of mesothelin-positive dysplastic cells in a subject in need thereof comprising administering an antibody that specifically binds to mesothelin and is capable of both eliciting an immune effector activity and internalizing within mesothelin-positive cells, the antibody comprising a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 2 absent amino acids 1 to 19 thereof and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 4 absent amino acids 1 to 19 thereof; a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 6 absent amino acids 1 to 19 thereof and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 8 absent amino acids 1 to 19 thereof; or a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 10 absent amino acids 1 to 19 thereof and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 12 absent amino acids 1 to 19 thereof.
2. The method of claim 1 wherein the dysplastic cells are ovarian carcinoma cells.
3. The method of claim 1 wherein the dysplastic cells are pancreatic adenocarcinoma cells.
4. The method of claim 1 wherein the dysplastic cells are mesothelioma cells.
5. The method of claim 1 wherein the dysplastic cells are lung carcinoma cells.
6. The method of claim 1 wherein the dysplastic cells are prostate cancer cells.
7. The method of claim 1 wherein the subject is a human.
8. The method of claim 1 wherein the antibody is conjugated to a chemotherapeutic agent.
9. The method of claim 1 further comprising administering to the subject a chemotherapeutic agent.
10. The method of claim 1 wherein the antibody is administered as an unconjugated antibody.
11. The method of claim 1 wherein the antibody is administered as a mixture of unconjugated antibody and antibody conjugated to a chemotherapeutic agent.