Bi-functional cancer treatment agents
View Patent ↗A novel fusion protein, comprising a receptor-antagonizing domain and a positive immunomodulator domain, characterized, for example, by its ability to block apoptosis and/or inhibit endocrine response, is useful in treating cancer. For example, a human prolactin antagonist-interleukin 2 (hPRLA-IL-2) fusion protein combines apoptosis induction and immuno-therapy to combat cancer in the breast or prostate.
1. A method for treating prostate and breast cancer, comprising administering to a patient that has prostate or breast cancer a protein that comprises a receptor-antagonizing domain and a positive immunomodulator domain, wherein the receptor-antagonizing domain comprises SEQ ID NO: 35 but has an amino acid substitution at position 129, and the positive immunomodulator domain is a cytokine selected from the group consisting of IL-2, IL-12, and IFNγ.
2. The method according to claim 1 , wherein the cytokine is IL-2.
3. The method according to claim 1 , wherein the cytokine is IL-12.
4. The method according to claim 1 , wherein the cytokine is IFNγ.
5. The method according to claim 1 , wherein cells of the cancer overexpress a prolactin receptor at levels greater than in normal, healthy cells.
6. A method for inducing an immune response in an individual that has cancerous prostate or breast cells, comprising administering to said individual a protein comprising (i) a prolactin-antagonist domain comprising SEQ ID NO: 35 but has an amino acid substitution at position 129, and (ii) an immunomodulatory domain, wherein said immunomodulatory domain is a cytokine selected from the group consisting of IL-2, IL-12, and INFγ.
7. The method of claim 6 , wherein said prolactin-antagonist domain comprises a protein consisting essentially of the amino acid sequence of SEQ ID NO. 34.
8. The method of claim 6 , wherein the amino acid at position 129 is arginine.
9. The method of claim 6 , wherein said cancerous cells express prolactin receptors at a level greater than that of normal, healthy cells.
10. The method of claim 6 , wherein said cytokine is IL-2.
11. The method of claim 6 , wherein said cytokine is IL-12.
12. The method of claim 6 , wherein said cytokine is IFNγ.
13. A method for inducing an immune response in an individual that has cancerous prostate or breast cells, comprising administering to said individual a protein comprising (i) a domain that binds to a receptor expressed on a cancer cell altering the function of said receptor, and (ii) another domain that elicits an immune response that is targeted to said cancer cell, wherein the domain that binds to a receptor expressed on a cancer cell is a prolactin antagonist domain comprising SEQ ID NO: 35 but has an amino acid substitution at position 129, and the domain that elicits an immune response is a cytokine selected from the group consisting of IL-2, IL-12, and IFNγ.
14. The method of claim 13 , wherein the prolactin-antagonist domain has an arginine at position 129.
15. The method of claim 14 , wherein the prolactin-antagonist domain comprises SEQ ID NO. 34.
16. The method of claim 1 , wherein the receptor antagonizing domain comprises SEQ ID NO: 34.
17. The method of claim 1 , wherein the amino acid at position 129 is a bulky side-chain amino acid.
18. The method of claim 6 , wherein the amino acid at position 129 is a bulky side-chain amino acid.
19. The method of claim 7 , wherein said cancerous cells express prolactin receptors at a level greater than that of normal, healthy cells.
20. The method of claim 7 , wherein said cytokine is IL-2.
21. The method of claim 7 , wherein said cytokine is IL-12.
22. The method of claim 7 , wherein said cytokine is IFNγ.