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1. (WO1991001753) INHIBITION OF TUMOR GROWTH BY BLOCKADE OF THE PROTEIN C SYSTEM
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We claim:
1. A composition for inhibition of tumor growth in a patient comprising:
a pharmaceutical carrier containing an effective dosage of a compound to block the protein C coagulation system.
2. The composition of claim 1 wherein the protein C blocking compound is selected from the group consisting of anti-protein C antibodies, anti-protein S antibodies, inactivated activated protein C and C4b binding protein.
3. The composition of claim 1 further comprising
a cytokine having at least one activity selected from the group consisting of stimulation of natural killer and lymphokine-activated killer cell-mediated cytotoxicity, activation of macrophages, stimulation of Fc receptor expression on mononuclear cells and antibody-dependent cellular cytotoxicity, enhancement of HLA class II antigen expression, and stimulation of procoagulant activity in a dosage facilitating hemorrhagic necrosis of the tumor in combination with the compound blocking the protein C system.
4. The composition of claim 3 wherein the cytokine is selected from the group consisting of tumor necrosis factor, gamma interferon, granulocyte-macrophage colony stimulating factor, interleukin-1 and interleukin-2.
5. The composition of claim 3 further comprising a
chemotherapeutic agent selectively inhibiting growth of rapidly replicating cells.
6. The composition of claim 1 further comprising endotoxin in a dosage stimulating production of tumor necrosis factor.
7. The composition of claim 3 in combination with a source of radiation causing inflammation of the tumor.
8. The composition of claim 3 in combination with a
chemotherapeutic agent inhibiting replication of cells.

9. The composition of claim 4 comprising anti-protein C antibodies in a dosage equal to or greater than the molar
concentration of protein C in the blood of the patient and tumor necrosis factor in a dosage delivering less than 100 μg TNF/kg body weight
10. The composition of claim 4 comprising anti-protein S antibodies in a dosage equal to or greater than the molar
concentration of protein S in the blood of the patient and tumor necrosis factor in a dosage delivering less than 100 μg TNF/kg body weight
l The composition of claim 4 comprising C4b binding protein in a dosage equal to or greater than five times the molar
concentration of C4b binding protein in the blood of the patient and tumor necrosis factor in a dosage delivering less than 100 μg TNF/kg body weight.
12. A method for inhibition of tumor growth in a patient comprising: •
administering a compound in a dosage blocking the protein C coagulation system and facilitating hemorrhagic necrosis of tumors.

13. The method of- claim 12 further comprising selecting the protein C blocking compound from the group consisting of anti-protein C antibodies, anti-protein S antibodies, inactivated activated protein C and C4b binding protein.
14. The method of claim 12 further comprising administering a cytokine having at least one activity selected from the group consisting of stimulation of natural killer and lymphokine-activated killer cell-mediated cytotoxicity, activation of macrophages, stimulation of Fc receptor expression on mononuclear cells and antibody-dependent cellular cytotdxicity, enhancement of HLA class II antigen expression, and stimulation of procoagulant activity, in a dosage facilitating hemorrhagic necrosis of the tumor in combination with the compound blocking the protein C coagulation system.

15. The method of claim 14 wherein the cytokine is selected from the group consisting of tumor necrosis factor, gamma interferon, granulocyte-macrophage colony stimulating factor, interleukin-1 and interleukin-2.
16. The method of claim 12 further comprising providing endotoxin in a dosage stimulating production of tumor necrosis factor.

17. The method of claim 13 wherein the protein C blocking compound is anti-protein C and the anti-protein C is administered in a dosage equal to or greater than the level of protein C in the blood.

18. The method of claim 17 wherein the dosage is equal to or greater than approximately 10 μg antibody/ml of blood.
19. The method of claim 13 wherein the protein C blocking compound is C4b binding protein and the C4b binding protein is administered in a dosage equal to or greater than five times the plasma levels of C4b binding protein.
20. The method of claim 13 wherein the protein C blocking compound is anti-protein S and the anti-protein S is administered in a dosage equal to or greater than the level of protein S in the blood.

21. The method of claim 20 wherein the dosage is equal to or greater than approximately 10 μg antibody/ml of blood.
22. The method of claim 14 wherein the protein C blocking compound and the cytokine are administered to the tumor.
23. The method of claim 14 further comprising administering a chemotherapeutic agent selectively inhibiting growth of rapidly replicating cells.
24. The method of claim 14 further comprising irradiating the patient to cause inflammation of the tumor.
25. The method of claim 14 further comprising using hypothermia to cause inflammation of the tumor.
26. The method of claim 14 wherein the protein C blocking compound and cytokine are administered intravenously.

27. The method of claim 14 wherein the protein C blocking compound and cytokine are aclministered in a single dosage.
28. The method of claim 12 further comprising administering a compound inhibiting blocking of the protein C system by the blocking agent
29. The method of claim 28 wherein the inhibitory compound is selected from the group consisting of protein C, activated protein C, protein S, and active site inactivated factor Xa.