Antibodies against cancer
An isolated binding partner of a Cripto-1 protein, Pim-1 protein or an antigen present in a colon cancer cell lysate is described. The binding partner inhibits growth of one or more cancer cell types and may be used in an anti-cancer agent for treating cancer in a subject. The binding partner may also be used in a method of inducing apoptosis in a cancer cell, as well as in a method of sensitizing a cancer cell to a cytotoxic compound. In addition, a cancer vaccine is described wherein the vaccine comprises a Cripto-1 protein (or an antigenic fragment thereof), Pim-1 protein (or an antigenic fragment thereof) or an antigen present in a colon cancer cell lysate or, alternatively, comprises an expressible DNA molecule encoding a Cripto-1 protein (or an antigenic fragment thereof), Pim-1 protein (or an antigenic fragment thereof) or an antigen present in a colon cancer cell lysate.
1. A method of treating cancer in a subject having cancer cells that over-express Cripto-1 as compared to non-cancerous cells, comprising administering to said subject a therapeutically effective amount of a monoclonal antibody or fragment thereof that binds a Cripto-1, whereby growth or spread of cancer cells in the subject is inhibited and wherein the mechanism of inhibition of growth or spread of the cancer cells is through:
(a) apoptosis induced by binding of the antibody or fragment thereof to the Cripto-1; or
(b) cytotoxicity induced by delivery to cancer cells of a cytotoxic compound conjugated to said monoclonal antibody or fragment thereof.
2. The method of claim 1 , wherein the monoclonal antibody or fragment thereof is a human monoclonal antibody or fragment thereof.
3. The method of claim 1 , wherein the monoclonal antibody or fragment thereof is a chimeric monoclonal antibody or fragment thereof.
4. The method of claim 1 , wherein the cancer is a colon cancer.
5. The method of claim 1 , wherein the cancer is a breast cancer.
6. The method of claim 1 , wherein the cancer is a prostate cancer.
7. The method of claim 1 , wherein the cancer is a leukemia.
8. The method of claim 1 , wherein the cancer is a lung cancer.
9. The method of claim 1 , wherein the antibody or fragment thereof induces apoptosis of cancer cells.
10. The method of claim 9 , wherein the antibody or fragment thereof induces apoptosis through activation of a JNK or p38 kinase cascade.
11. The method of claim 1 , wherein the antibody or fragment thereof binds to an antigenic determinant of Cripto-1 protein comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID: 2.
12. The method of claim 1 , wherein the mechanism of inhibition of grow or spread of cancer cells is apoptosis.
13. The method of claim 1 , wherein the mechanism of inhibition of growth or spread of cancer cells is cytotoxicity.
14. The method of claim 13 , wherein the antibody or fragment thereof is conjugated to a cytotoxic compound.
15. The method of claim 14 , wherein the cytotoxic compound is selected from the group consisting of anthracyclines, 5-fluorouracil, topoisomerase inhibitors, cisplatin, carboplatin and taxol.
16. The method of claim 15 , wherein the cytotoxic compound is an anthracycline selected from the group consisting of idarubicin, doxorubicin, daunorubicin and epirubicin.
17. The method of claim 16 , wherein the cytotoxic compound is the topoisomerase inhibitor irinotecan.