# US 5,348,739 A · Combined anti-tumor therapy with interleukin-2 and histamine, analogs thereof or H.sub.2 -receptor agonists > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,348,739 A - Document ID: US5348739A - Status: Granted - Kind: A - Application number: 07/843,052 - Filed: 1992-03-02 - Granted: 1994-09-20 - Earliest claimed: 1989-09-19 - Assignees: Suntello, Inc. - Inventors: Jan U. K. Hellstrand; Svante H. Hermodsson - Web page: https://patentgrep.com/patent/US5348739A ## CPC - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 38/2013: {IL-2} - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A method of inhibiting the development of malignant tumors and the formation of metastases of malignant tumor cells in a subject carrying the comprises administering to the subject IL-2 and an agent selected from the group consisting of histamine, a histamine structural analogs having H.sub.2 -receptor activities, an endogenous histamine releasing preparation, and a non-histamine derivative H.sub.2 -receptor agonist; the agent and the IL-2 being administered in amounts and for a time effective to attain the desired effect. A method of increasing the anti-tumor cell effect of IL-2 in a subject comprises co-administering to the subject IL-2 and an agent such as histamine, histamine structural analogs having H.sub.2 -receptor activities, endogenous histamine releasing preparations or H.sub.2 -receptor agonists, the agent and the IL-2 being administered in anti-tumor effective amounts and for a period of time effective to attain the desired effect. ## Claims ### Claim 1 A method of augmenting natural killer cell cytotoxicity in a subject carrying malignant tumor cells, comprising administering to the subject: a first composition comprising an agent selected from the group consisting of histamine, a histamine structural analog having H.sub.2 -receptor activities, an endogenous histamine releasing preparation and a non-histamine derivative H.sub.2 -receptor agonist; and a second composition comprising interleukin-2; said agent and said interleukin-2 being administered in amounts and for a period of time effective to augment natural killer cell cytotoxicity. ### Claim 2 (depends on 1) The method of claim 1, wherein the agent is administered in an amount of 1 to 10 mg/day. ### Claim 3 (depends on 1) The method of claim 1, wherein the agent is administered for a period of time of 1 to 4 weeks. ### Claim 4 (depends on 1) The method of claim 1, wherein the interleukin-2 is administered in an amount of 5,000 to 300,000 U/kg/day. ### Claim 5 (depends on 1) The method of claim 1, wherein the interleukin-2 is administered for a period of time of 1 day to 4 weeks. ### Claim 6 (depends on 1) The method of claim 1, wherein the agent and the interleukin-2 are administered on the same days. ### Claim 7 (depends on 1) The method of claim 1, wherein the agent is histamine. ### Claim 8 In a method of treating a subject carrying malignant tumor cells with a composition comprising interleukin-2, the improvement comprising: co-administering to the subject, with the interleukin-2, a composition comprising an agent selected from the group consisting of histamine, a histamine structural analog having H.sub.2 -receptor activities, an endogeneous histamine releasing preparation and a non-histamine derivative H.sub.2 -receptor agonist; the interleukin-2 and the agent being administered in amounts and for a period of time effective to augment natural killer cell cytotoxicity. ### Claim 9 (depends on 8) The method of claim 8, wherein the agent is administered in an amount of 1 to 10 mg/day. ### Claim 10 (depends on 8) The method of claim 8, wherein the agent is administered for a period of time of 1 day to 4 weeks. ### Claim 11 (depends on 8) The method of claim 8, wherein the interleukin-2 is administered in an amount of 5,000 to 300,000 U/kg/day. ### Claim 12 (depends on 8) The method of claim 8, wherein the interleukin-2 is administered for a period of time of 1 day to 4 weeks. ### Claim 13 (depends on 8) The method of claim 8, wherein the agent and the interleukin-2 are administered on the same days. ### Claim 14 (depends on 8) The method of claim 8, wherein the agent is histamine. ### Claim 15 A method for augmenting natural killer cell cytotoxicity comprising the steps of: administering the following to a population of cells which includes lymphocytes and monocytes: (a) an effective amount f interleukin-2; and (b) a compound selected from the group consisting histamine, histamine structural analog having H.sub.2 -receptor activities, an endogenous histamine releasing preparation and a non-histamine derivative H.sub.2 -receptor agonist. ### Claim 16 (depends on 15) The method of claim 15, wherein said population of cells is located in vitro. ### Claim 17 (depends on 15) The method of claim 15, wherein said population of cells is located in vivo. ### Claim 18 (depends on 15) The method of claim 15, wherein the administration of said interleukin-2 and said compound is performed simultaneously. ### Claim 19 (depends on 15) The method of claim 15, wherein the administration of said interleukin-2 and said compound is performed on the same day. ### Claim 20 (depends on 17) The method of claim 17, wherein the interleukin-2 is administered in an amount of from 5,000 to 300,000 U/kg/day. ### Claim 21 (depends on 17) The method of claim 17, wherein the interleukin-2 is administered of a period of time from 1 day to about 4 weeks. ### Claim 22 (depends on 17) The method of claim 17, wherein the compound is administered in an amount of 1 to 10 mg/day. ### Claim 23 (depends on 17) The method of claim 17, wherein the compound is administered for a period of time from 1 day to 4 weeks.