Method treating malignant ascites and metastatic pleural effusion with and disulfide-linked trimeric TRAIL
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 of treating metastatic pleural effusion in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of a disulfide bond-linked trimeric TRAIL fusion protein, wherein the disulfide bond-linked trimeric TRAIL fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1 or SEQ ID NO: 2.
2. The method of claim 1 , wherein the disulfide bond-linked trimeric TRAIL fusion protein is administered via intra-pleural infusion.
3. The method of claim 1 , wherein the disulfide bond-linked trimeric TRAIL fusion protein is administered in combination with an immune checkpoint inhibitor.
4. The method of claim 3 , wherein the immune checkpoint inhibitor is an anti-PD-1 antibody.
5. The method of claim 3 , wherein the immune checkpoint inhibitor is an anti-PD-L1 antibody.
6. The method of claim 1 , wherein the disulfide bond-linked trimeric TRAIL fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 2.
7. The method of claim 1 , wherein the disulfide bond-linked trimeric TRAIL fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1.
8. A method of treating malignant ascites in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of a disulfide bond-linked trimeric TRAIL fusion protein in combination with an immune checkpoint inhibitor, wherein the disulfide bond-linked trimeric TRAIL fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1 or SEQ ID NO: 2.
9. The method of claim 8 , wherein the immune checkpoint inhibitor is an anti-PD-1 antibody.
10. The method of claim 8 , wherein the immune checkpoint inhibitor is an anti-PD-L1 antibody.
11. The method of claim 8 , wherein the disulfide bond-linked trimeric TRAIL fusion protein is administered via intraperitoneal infusion.
12. The method of claim 8 , wherein the disulfide bond-linked trimeric TRAIL fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 2.
13. The method of claim 8 , wherein the disulfide bond-linked trimeric TRAIL fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1.