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. An isolated nucleic acid encoding a heavy chain and a light chain of an antibody that specifically binds to mesothelin, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 2 absent amino acids 1 to 19 thereof, SEQ ID NO: 6 absent amino acids 1 to 19 thereof, or SEQ ID NO: 10 absent amino acids 1 to 19 thereof, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 4 absent amino acids 1 to 19 thereof, SEQ ID NO: 8 absent amino acids 1 to 19 thereof, or SEQ ID NO: 12 absent amino acids 1 to 19 thereof.
2. The isolated nucleic acid of claim 1 , wherein said heavy chain is encoded by a nucleic acid sequence comprising SEQ ID NO: 1 absent nucleotides 1 to 57 thereof, SEQ ID NO: 5 absent nucleotides 1 to 57 thereof, or SEQ ID NO: 9 absent nucleotides 1 to 57 thereof, respectively, and wherein said light chain is encoded by a nucleic acid sequence comprising SEQ ID NO: 3 absent nucleotides 1 to 57 thereof, SEQ ID NO: 7 absent nucleotides 1 to 57 thereof, or SEQ ID NO: 11 absent nucleotides 1 to 57 thereof, respectively.
3. A vector comprising the nucleic acid of claim 1 .
4. An isolated cell comprising the nucleic acid of claim 1 .
5. A recombinant nucleic acid encoding a heavy chain and a light chain of an antibody that specifically binds to mesothelin, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 2 absent amino acids 1 to 19 thereof, SEQ ID NO: 6 absent amino acids 1 to 19 thereof, or SEQ ID NO: 10 absent amino acids 1 to 19 thereof, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 4 absent amino acids 1 to 19 thereof, SEQ ID NO: 8 absent amino acids 1 to 19 thereof, or SEQ ID NO: 12 absent amino acids 1 to 19 thereof.
6. The recombinant nucleic acid of claim 5 , wherein said heavy chain is encoded by the nucleic acid sequence comprising SEQ ID NO: 1 absent nucleotides 1 to 57 thereof, SEQ ID NO: 5 absent nucleotides 1 to 57 thereof, or SEQ ID NO: 9 absent nucleotides 1 to 57 thereof, respectively, and wherein said light chain is encoded by the nucleic acid sequence comprising SEQ ID NO: 3 absent nucleotides 1 to 57 thereof, SEQ ID NO: 7 absent nucleotides 1 to 57 thereof, or SEQ ID NO: 11 absent nucleotides 1 to 57 thereof, respectively.
7. A vector comprising the nucleic acid of claim 5 .
8. An isolated cell comprising the nucleic acid of claim 5 .
9. A recombinant cell that produces an 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.