Stable circulating histamine levels
AssigneeMaxim Pharmaceuticals, Inc.
InventorsKristoffer Hellstrand, Svante Hermodsson
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Abstract
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.
Claims37
A method of augmenting the activity of an agent which enhances natural killer cell cytotoxicity comprising:
- a) administering a plurality of doses of histamine in a pharmaceutically acceptable form over a period of at least 1 week prior to administration of said agent such that a stable, circulating blood histamine concentration sufficient to augment the cytotoxicity enhancing effect of said agent is achieved;
- and
- b) administering a beneficial amount of said agent after said stable, circulating blood histamine concentration is achieved, wherein the cytotoxicity enhancing effects of said agent are augmented.
A method of treating a subject having a malignancy with histamine and a second beneficial agent wherein the activity of said second beneficial agent is augmented by histamine comprising:
- a) administering a plurality of doses of histamine in a pharmaceutically acceptable form at least 1 week prior to administration of said second beneficial agent such that a stable, circulating beneficial blood histamine level is achieved;
- and
- b) administering said second beneficial agent after said stable beneficial histamine level is achieved.
A method of enhancing the cytotoxic activity of natural killer cells comprising:
- a) measuring blood histamine levels in a subject to determine whether the cytotoxic activity of said subject's natural killer cells could be enhanced by increasing the levels of blood histamine in said subject;
- b) administering a plurality of doses of histamine in a pharmaceutically acceptable form to a subject for whom said measuring step indicated that the cytotoxic activity of said subject's natural killer cells could be enhanced by increasing said subject's blood histamine levels, such that stable beneficial levels of circulating blood histamine are achieved;
- and
- c) administering a second agent to said subject having beneficial levels of blood histamine, such that the cytotoxic activity of said subject's natural killer cells is enhanced, wherein said second agent is administered at least one week subsequent to administration of said plurality of doses of histamine.
A method of treating a malignancy comprising:
- a) providing a beneficial stable level of circulating blood histamine in a subject having a malignancy at least one week prior to subsequent chemotherapy by administering a plurality of doses of histamine in a pharmaceutically acceptable form sufficient to attain said beneficial stable level of circulating blood histamine;
- and
- b) treating the subject having a malignancy with a chemotherapeutic agent after said beneficial stable level of circulating blood histamine is attained.
A method of treating a subject having a malignancy, comprising:
- administering to said subject a plurality of doses of histamine in a pharmaceutically acceptable form;
- determining when a stable circulating histamine level has been achieved in the subject;
- and
- administering to the subject, in response to achievement of stable circulating histamine level, an agent that stimulates the cytotoxicity of natural killer cells at least one week subsequent to achieving said stable circulating histamine level.
Dependencies are inferred from the claim text.