Method and system to remove cytokine inhibitor in patients

• US 20050244371A1
• Filed: 06/14/2005
• Published: 11/03/2005
• Est. Priority Date: 05/22/1998
• Status: Abandoned Application

• Current Assignee: Innatus Corporation
• Original Assignee: Biopheresis Technologies Incorporated
• Inventors: Lentz, M. Rigdon
• Application Number:
  US11/153,524
• Publication Number:
  US 20050244371A1
• Time in Patent Office: Days
• US Class Current: 424/85.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 41/17 by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
• CPC Class Codes: A61M 1/34 Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
• CPC Class Codes: A61M 1/342 Adding solutions to the blood, e.g. substitution solutions for preventing coagulation A61M1/3672
• CPC Class Codes: A61M 1/3441 Substitution rate control as a function of the ultrafiltration rate
• CPC Class Codes: A61M 1/3468 using treated filtrate as substitution fluid
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3482 by filtrating the filtrate using another cross-flow filter, e.g. a membrane filter
• CPC Class Codes: A61M 1/3486 Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
• CPC Class Codes: A61M 1/3496 Plasmapheresis; Leucopheresis; Lymphopheresis A61M1/3472 takes precedence
• CPC Class Codes: A61M 2202/0417 Immunoglobulin
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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.

Claims

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.

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.

6. (canceled)

12-16. -16. (canceled)