Maxim Pharmaceuticals, Inc.

Svante Hermod Hermodsson

Kristoffer Hellstrand

Kurt R Gehlsen

Jan Urban Hellstrand

Jan Urban Kristoffer Hellstrand

Disclosed is a method of promoting the maturation of monocytes comprising the administration of a reactive oxygen species (ROS) inhibitor or scavenger and at least one monocyte maturation-promoting agent. A composition for promoting the maturation of monocytes is likewise disclosed. The pharmaceutical composition includes a compound effective to promote the maturation of monocytes and a ROS inhibitor or scavenger combined in a pharmaceutically acceptable carrier.

Methods and compositions for promoting the maturation of monocytes

The present invention relates to a method for preventing and/or reducing cellular and tissue damage caused by reactive oxygen metabolites (ROMs) released by phagocytic or endothelial cells in response to various disease states or pathologies. The methods of the present invention are useful in preventing and treating a variety of disease states or pathological situations in which ROMs are produced and released. The methods of the present invention contemplate reducing ROM-mediated damage by reducing the production and release of ROMs.

Treatment and prevention of reactive oxygen metabolite-mediated cellular damage

Methods for obtaining beneficial stable levels of circulating histamine are disclosed for use in methods for enhancing natural killer cell cytotoxicity and for elevating histamine levels in individuals in need thereof. In such methods, a beneficial level of circulating histamine is attained and an agent whose ability to enhance natural killer cell cytotoxicity is augmented by histamine is administered. Alternatively, stable beneficial levels of circulating histamine can be attained in subjects receiving chemotherapy or antiviral treatment. The invention may also be employed in treatments combining histamine, agents which enhance natural killer cell cytotoxicity, and chemotherapeutic agents. Optimization of the delivery of histamine and substances which induce the release of endogenous histamine are also disclosed.

Elevation of circulating blood histamine levels

The present invention relates to methods of treating cancer in which histamine is administered in conjunction with other cancer therapies. The cancer therapy includes surgery, radiation, immunotherapy, the administration of an agent which enhances the humoral immune response of the patient or any combination thereof.

Synergistic tumorcidal response induced by histamine

The present invention relates to a method for preventing and/or reducing cellular and tissue damage caused by reactive oxygen metabolites (ROMs) released by phagocytic or endothelial cells in response to various infectious disease states or pathologies. The methods of the present invention contemplate reducing ROM-mediated damage by reducing the production and release of ROMs.

A method for providing activated natural killer (NK) cells comprising the steps of administering to a population of cells which includes lymphocytes and monocytes, an effective amount of an NK cell activating cytokine or a NK cell activating flavonoid, wherein said NK cell activating cytokine is not IL-2 or IFN-&agr;; and administering a compound effective to inhibit the production or release of hydrogen peroxide selected from the group consisting of histamine, other H receptor agonists, and serotonin.

Enhanced activation of natural killer cells using an NK cell activator and a hydrogen peroxide scavenger or inhibitor

In a method of treating a viral infection involving activation of NK cells, the improvement comprising administering to a patient receiving such treatment an effective NK-cell-activity facilitating amount of a histamine H,or 5-HT,receptor agonist.

Method for treatment of cancer and infectious disease

A method for treating neoplastic disease comprising the steps of: administering to a patient receiving radiation therapy or chemotherapy, an effective amount of an NK cell activating cytokine or an NK cell activating flavonoid, wherein said NK cell activating cytokine is not IL-2 or IFN-&agr;; and administering to the patient a compound effective to inhibit the production or release of intracellular hydrogen peroxide selected from the group consisting of histamine, other H,receptor agonists, and serotonin.

Enhanced activation of natural killer cells using an NK cell activator and hydrogen peroxide scavenger or inhibitor

Methods for obtaining beneficial stable levels of circulating histamine are disclosed for use in methods for enhancing natural killer cell cytotoxicity. In such methods, a beneficial level of circulating histamine is attained and an agent whose ability to enhance natural killer cell cytotoxicity is augmented by histamine is administered. Alternatively, stable beneficial levels of circulating histamine can be attained in subjects receiving chemotherapy or antiviral treatment. The invention may also be employed in treatments combining histamine, agents which enhance natural killer cell cytotoxicity, and chemotherapeutic agents. Optimization of the delivery of histamine and substances which induce the release of endogenous histamine are also disclosed.

Administration of histamine for therapeutic purposes

Method for treatment of cancer and infectious disease comprises administering a first composition containing interferon-.alpha. or analogues thereof, together with a second composition containing at least one substance with H.sub.2, or 5-HT.sub.1A, receptor agonist activity, for example, histamine or serotonin. The first and second compositions are either mixed in a preparation or furnished in separate doses.

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Molndal, Sweden

Svante Hermod Hermodsson