Therapeutic binding agents against MUC-1 antigen and methods for their use
View Patent ↗The invention provides therapeutic compositions comprising binding agents that specifically bind to tumor-associated MUC-1 and reduce, reverse or prevent their effects in cancer. More particularly, the invention provides therapeutic compositions that comprise a binding agent that can specifically bind to an epitope that comprises both peptide and carbohydrate on such tumor-associated MUC-1. The invention further provides methods for the use of such therapeutic compositions in the treatment of cancer. The invention also provides methods for therapeutically treating a mammal bearing a tumor comprising administering to the mammal an effective amount of a therapeutic composition consisting essentially of a binding agent that specifically binds to an epitope of tumor-associated MUC1, wherein the mammal generates an immune response that comprises an antibody that specifically binds to an epitope of tumor-associated MUC1 that is different from the epitope of tumor associated MUC1 that is specifically bound by the binding agent.
1. A method for therapeutically treating a mammal bearing a tumor, the method comprising generating an immune response by administering to the mammal an effective amount of a therapeutic composition consisting essentially of an antibody or antigen binding fragment thereof that binds to an epitope of MUC-1, the epitope comprising a peptide and a carbohydrate, wherein the peptide consists of the amino acid sequence DTRPAP (SEQ ID NO:5), and wherein the antibody or antigen binding fragment thereof binds preferentially to glycosylated MUC-1.
2. The method of claim 1 , wherein the antibody or fragment thereof that binds to an epitope of MUC-1 is non-radiolabeled.
3. The method of claim 1 , wherein the immune response includes a T cell response.
4. The method of claim 1 , wherein the mammal is a human.
5. The method of claim 1 , wherein the therapeutic composition is administered intravenously.
6. The method of claim 1 , wherein the therapeutic composition is administered subcutaneously.
7. The method of claim 1 , wherein the antibody or antigen binding fragment thereof in the therapeutic composition is administered at a dosage of less than 8 mg/30 kg body weight.
8. The method of claim 1 , wherein the antibody or antigen binding fragment in the therapeutic composition is administered at a dosage of less than 3 mg/30 kg body weight.
9. The method of claim 1 , wherein the antibody or antigen binding fragment in the therapeutic composition is administered at a dosage of about 2 mg/patient.
10. A method for inducing the production of antibodies against the multi-epitopic antigen MUC-1 comprising administering to the mammal an effective amount of a composition consisting essentially of an antibody or antigen binding fragment thereof that specifically binds to a first epitope of MUC-1 such that the mammal generates an immune response comprising antibodies against a second epitope of MUC-1, wherein the antibody or antigen binding fragment thereof in the composition binds to a first epitope of MUC-1 comprising a peptide and a carbohydrate, wherein the peptide consists of the amino acid sequence DTRPAP (SEQ ID NO:5), and wherein the antibody or antigen binding fragment thereof in the composition binds preferentially to glycosylated MUC-1.
11. The method of claim 10 , wherein the antibody or antigen binding fragment thereof is non-radiolabeled.
12. A method for therapeutically treating a mammal bearing a tumor comprising administering to the mammal an effective amount of a therapeutic composition consisting essentially of an antibody or antigen binding fragment thereof that specifically binds to a first epitope on the multi-epitopic antigen MUC-1 such that the mammal generates an immune response against a second epitope on the multi-epitopic antigen MUC-1, wherein the antibody or antigen binding fragment thereof in the composition binds to a first epitope of MUC-1 comprising a peptide and a carbohydrate, wherein the peptide consists of the amino acid sequence DTRPAP (SEQ ID NO:5), wherein the antibody or antigen binding fragment thereof in the composition binds preferentially to glycosylated MUC-1, and wherein the antibody is not a monoclonal antibody selected from: HMPV, VU-3-C6, MF06, VU-11-D1, MF30, BCP8, DF3, BC2, B27.29, VU-3-D1, 7540MR, MF11, Bc4E549, VU-11-E2, M38, E29, GP1.4, 214D4, BC4W154, HMFG-2, HMFG-1, C595, Mc5 and A76-A/C7.
13. The method of claim 10 or 12 , wherein the immune response includes a T cell response.
14. The method of claim 10 or 12 , wherein the antibody is Alt-1.
15. The method of claim 10 or 12 , wherein the mammal is a human.
16. The method of claim 10 or 12 , wherein the composition is administered intravenously.
17. The method of claim 10 or 12 , wherein the composition is administered subcutaneously.
18. The method of claim 10 or 12 , wherein the antibody or antigen binding fragment thereof in the composition is administered at a dosage of less than 8 mg/30 kg body weight.
19. The method of claim 10 or 12 , wherein the antibody or antigen binding fragment thereof in the composition is administered at a dosage of less than 3 mg/30 kg body weight.
20. The method of claim 10 or 12 , wherein the antibody or antigen binding fragment thereof in the composition is administered at a dosage of about 2 mg/patient.
21. The method of claim 10 or 12 , wherein the antibody or antigen binding fragment thereof is selected from a monoclonal antibody, a chimeric antibody, a genetically engineered antibody, a Fab fragment, a F(ab′) 2 fragment, and a single chain antibody.
22. The method of claim 1 wherein the antibody is Alt-1.
23. The method of claim 12 , wherein the antibody or antigen binding fragment thereof is non-radiolabeled.