Method for treating cancer using disulfide-linked trimeric 4-1BBL
Compositions of TNF family of cytokines in covalently linked trimeric forms are disclosed. The resulting fusion proteins are secreted as disulfide bond-linked homotrimers, which are more stable in structure and therapeutically more efficacious than their native counterparts.
1. A method for treating cancer in a mammal, comprising a step of administering to said mammal a therapeutically effective amount of a disulfide bond-linked trimeric 4-1BBL fusion protein, wherein the disulfide bond-linked trimeric 4-1BBL the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4.
2. The method of claim 1 , wherein the administering step further comprises administration of a therapeutically effective amount of an anti-PD1 antibody along with the therapeutically effective amount of the disulfide bond-linked trimeric 4-1BBL fusion protein.
3. The method of claim 1 , wherein the administering step further comprises administration of a therapeutically effective amount of an anti-PD-L1 antibody along with the therapeutically effective amount of the disulfide bond-linked trimeric 4-1BBL fusion protein.
4. The method of claim 1 , wherein the cancer is gastrointestinal cancer.
5. The method of claim 1 , wherein the cancer is colorectal cancer.
6. The method of claim 1 , wherein the cancer is lung cancer.
7. The method of claim 1 , wherein the cancer is pancreatic cancer.
8. The method of claim 1 , wherein the cancer is ovarian cancer.
9. The method of claim 1 , wherein the cancer is a malignant ascites.
10. The method of claim 1 , wherein the cancer is peritoneal carcinomatosis.
11. The method of claim 1 , wherein the disulfide bond-linked trimeric fusion protein is administered via intravenous injection.
12. The method of claim 1 , wherein the disulfide bond-linked trimeric fusion protein is administered via intraperitoneal infusion.
13. The method of claim 1 , wherein the disulfide bond-linked trimeric fusion protein is administered via intra-pleural infusion.
14. The method of claim 1 , wherein the disulfide bond-linked trimeric fusion protein is administered via subcutaneous injection.
15. The method of claim 1 , wherein the disulfide bond-linked trimeric fusion protein is administered in a series of doses separated by intervals of days or weeks.
16. The method of claim 1 , wherein the disulfide bond-linked trimeric fusion protein is administered in combination with chemotherapy.
17. The method of claim 1 , wherein the disulfide bond-linked trimeric fusion protein is administered in combination with a Ras inhibitor.