Compositions and methods for detection and treatment of cancer
Novel antibodies for the detection and/or treatment of a cancer (e.g., a pancreatic cancer or an ovarian cancer) are provided. In certain embodiments the antibodies bind a region of the MUC4 protein that does not comprise the central tandem repeat (TR) domain of MUC4. Certain antibodies bind to the MUC4 peptide fragment MUC4-α-N-Ter and/or to the MUC4 peptide fragment MUC4-α-C-Ter. Chimeric constructs comprising such antibodies are also provided.
1. An isolated monoclonal antibody that binds a region of the MUC4 protein that does not comprise the central tandem repeat (TR) domain of MUC4, wherein said antibody binds to a peptide consisting of the amino acid sequence of MUC4-α-N-Ter (SEQ ID NO: 1), or to a peptide consisting of the amino acid sequence of MUC4-α-C-Ter (SEQ ID NO: 2).
2. The antibody of claim 1 , wherein said antibody binds to the peptide consisting of the amino acid sequence of MUC4-α-N-Ter (SEQ ID NO: 1).
3. The antibody of claim 1 , wherein said antibody binds to the peptide consisting of the amino acid sequence of MUC4-α-C-Ter (SEQ ID NO: 2).
4. The antibody of claim 1 , wherein said antibody does not bind the central tandem repeat (TR) domain of MUC4.
5. The antibody of claim 1 , wherein said antibody also binds to a cell that expresses a MUC4 protein.
6. The antibody of claim 5 , wherein said cell is a cancer cell.
7. The antibody of claim 1 , wherein said antibody is a monoclonal antibody or a fragment thereof.
8. The antibody of claim 7 , wherein said antibody is an IgG or a fragment thereof, or an IgM or a fragment thereof.
9. The antibody of claim 1 , wherein said antibody is produced by immunization of a non-human mammal with the MUC4-α-N-Ter and/or MUC4-α-C-Ter.
10. The antibody of claim 1 , wherein said antibody is a humanized antibody.
11. The antibody of claim 1 , wherein said antibody is attached to an effector.
12. The antibody of claim 11 , wherein said effector is an effector selected from the group consisting of a cytokine, an epitope tag, a second antibody a detectable label, an anti-cancer drug, a delivery vehicle comprising an anti-cancer drug, a cytotoxin, a radionuclide, a prodrug, a viral particle, a radiosensitizer, and a chelate.
13. A pharmaceutical formulation said formulation comprising: a pharmaceutically acceptable excipient; and an isolated monoclonal antibody that binds a region of the MUC4 protein that does not comprise the central tandem repeat (TR) domain of MUC4, wherein said antibody binds to a peptide consisting of the amino acid sequence of MUC4-α-N-Ter (SEQ ID NO: 1), or to a peptide consisting of the amino acid sequence of MUC4-α-C-Ter (SEQ ID NO: 2).
14. The pharmaceutical formulation of claim 13 , wherein said antibody binds to the peptide consisting of the amino acid sequence of MUC4-α-N-Ter (SEQ ID NO: 1).
15. The pharmaceutical formulation of claim 13 , wherein said antibody binds to the peptide consisting of the amino acid sequence of MUC4-α-C-Ter (SEQ ID NO: 2).
16. A pharmaceutical formulation said formulation comprising: a pharmaceutically acceptable excipient; and an isolated monoclonal antibody that binds a region of the MUC4 protein that does not comprise the central tandem repeat (TR) domain of MUC4, wherein said antibody binds to a peptide consisting of the amino acid sequence of MUC4-α-N-Ter (SEQ ID NO: 1), or to a peptide consisting of the amino acid sequence of MUC4-α-C-Ter (SEQ ID NO: 2) wherein said antibody is attached to an effector.
17. The pharmaceutical formulation of claim 16 , wherein said effector is an effector selected from the group consisting of a cytokine, an epitope tag, a second antibody a detectable label, an anti-cancer drug, a delivery vehicle comprising an anti-cancer drug, a cytotoxin, a radionuclide, a prodrug, a viral particle, a radiosensitizer, and a chelate.