Method and system to remove cytokine inhibitor in patients

Abstract

A method to treat cancer uses ultrapheresis, refined to remove compounds of less than 120,000 daltons molecular weight, followed by administration of replacement fluid, to stimulate the patient's immune system to attack solid tumors. In the preferred embodiment, the patient is ultrapheresed using a capillary tube ultrafilter having a pore size of 0.02 to 0.05 microns, with a molecular weight cutoff of 120,000 daltons, sufficient to filter one blood volume. The preferred replacement fluid is ultrapheresed normal plasma. The patient is preferably treated daily for three weeks, diagnostic tests conducted to verify that there has been shrinkage of the tumors, then the treatment regime is repeated. The treatment is preferably combined with an alternative therapy, for example, treatment with an anti-angiogenic compound, one or more cytokines such as TNF, gamma interferon, or IL-2, or a procoagulant compound. The treatment increases endogenous, local levels of cytokines, such as TNF. This provides a basis for an improved effect when combined with any treatment that enhances cytokine activity against the tumors, for example, treatments using alkylating agents, doxyrubicin, carboplatinum, cisplatinum, and taxol. Alternatively, the ultrapheresis treatment can be combined with local chemotherapy, systemic chemotherapy, and/or radiation.

1 . A method for inducing an immune response against transformed, infected or diseased tissue in a patient comprising 
 contacting the blood, plasma or one or more components of the blood of a patient in need thereof with a column or filter having immobilized therein molecules binding to soluble cytokine receptor molecules, wherein the cytokine is selected from the group consisting of GM-CSF, erythropoietin, thrombopoetin, G-CSF, M-CSF and SCF, wherein the binding molecules are selected from the group consisting of antibodies or antibody fragments and soluble cytokine molecules, wherein binding of the soluble cytokine receptors prevents the soluble cytokine receptors from binding to cytokines in the tissue to be treated, until an immune response is induced in the transformed, infected, or diseased tissue.    
     
     
         2 . The method of  claim 1  wherein the tissue is a solid tumor.  
     
     
         3 . The method of  claim 1  wherein the disease is a viral or parasitic disease causing immunosuppression.  
     
     
         4 . The method of  claim 1  wherein the molecule is an antibody to the soluble cytokine receptor.  
     
     
         5 . The method of  claim 1  further comprising treating the tissue with an agent selected from the group consisting of anti-angiogenic compounds, procoagulant compounds, cytokines, chemotherapeutic agents, and radiation.  
     
     
         6 . (canceled)  
     
     
         7 . The method of  claim 1  wherein the soluble cytokine receptor molecules are selected from the group consisting of soluble tissue factor receptor 1 (“sTNFR-1”) and soluble tissue necrosis factor receptor-2 (“sTNFR-2”).  
     
     
         8 . The method of  claim 1  wherein the cytokine receptor molecules are removed by binding to antibodies or antibody fragments immunoreactive with the cytokine receptor molecules.  
     
     
         9 . The method of  claim 8  wherein the soluble cytokine receptor molecules or antibodies or antibody fragments are immobilized in a filter or column through which the patient's blood or plasma or one or more components thereof is circulated prior to being returned to the patient.  
     
     
         10 . The method of  claim 4  wherein the antibodies are humanized.  
     
     
         11 . The method of  claim 1  comprising 
 contacting the blood, plasma or components thereof with antibodies or antibody fragments immobilized in a sterile endotoxin free extracorporeal device.    
     
     
         12 - 16 . (canceled)