Glucocerebroside treatment of disease
AssigneeEnzo Therapeutics, Inc.
InventorsYaron Iian, Maya Margalit, Ari Zimran
Life of this patent
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Abstract
The present invention provides a method for the treatment of immune mediated or immune related diseases or disorders, infectious diseases, metabolic disorders and cancer in mammalian subjects. This method comprises the administration of a naturally occurring, mammalian intermediary metabolite or T cell receptor ligand, preferably a glucosylceramide, to a mammalian subject. In a preferred embodiment, such mammalian subjects are human beings.
Claims113
A method for the treatment of a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject an effective amount of a T cell ligand.
An in vitro screening assay for an analogue or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a disease comprising:
- a) providing in vitro:
- (i) regulatory, immune-regulatory or NKT cells from said subject or another subject;
- (ii) antigen presenting cells;
- (iii) analogue or derivative of said intermediary metabolite;
- and
- b) identifying a decrease in said regulatory, immune-regulatory or NKT cell proliferation.
An in vitro screening assay for an analogue or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a disease comprising:
- a) providing in vitro:
- i) regulatory, immune-regulatory or NKT cells and BSA in a first test tube;
- ii) regulatory, immune-regulatory or NKT cells and said analogue or derivative of an intermediary metabolite in a second test tube;
- iii) regulatory, immune-regulatory or NKT cells, antigen presenting cells and BSA in a third test tube;
- iv) regulatory, immune-regulatory or NKT cells, antigen-presenting cells and an analogue or derivative of said intermediary metabolite;
- b) determining the amount of regulatory, immune-regulatory or NKT cell proliferation in each of said tubes;
- and
- c) identifying the least amount of regulatory, immune-regulatory or NKT cell proliferation in said fourth tube.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) intermediary metabolite;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- and
- b) re-administering to said subject said treated or educated cells.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) intermediary metabolite;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- c) re-administering to said subject said treated or educated cells;
- and
- d) administering to said subject:
- i) an effective amount of an intermediary metabolite;
- ii) antigen presenting cells;
- iii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- iv) any combination of the above.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject:
- a) an effective amount of an intermediary metabolite;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
A therapeutic composition for the treatment of a disease in a mammalian subject comprising:
- a) an intermediary metabolite;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
An in vitro screening assay for an analogue or derivative of a T cell receptor ligand comprising:
- a) providing in vitro:
- (i) regulatory, immune-regulatory or NKT cells from said subject or another subject;
- (ii) antigen presenting cells;
- (iv) analogue or derivative of said T cell receptor ligand;
- b) identifying a decrease in said regulatory, immune-regulatory or NKT cell proliferation.
An in vitro screening assay for an analogue or derivative of a T cell receptor ligand which is administered to a mammalian subject to treat a disease comprising:
- a) providing in vitro:
- i) regulatory, immune-regulatory or NKT cells and BSA in a first test tube;
- ii) regulatory, immune-regulatory or NKT cells and said analogue or derivative of a T cell receptor ligand in a second test tube;
- iii) regulatory, immune-regulatory or NKT cells, antigen presenting cells and BSA in a third test tube;
- iv) regulatory, immune-regulatory or NKT cells, antigen-presenting cells and an analogue or derivative of said T cell receptor ligand;
- b) determining the amount of regulatory, immune-regulatory or NKT cell proliferation in each of said tubes;
- and
- c) identifying the least amount of regulatory, immune-regulatory or NKT cell proliferation in said fourth tube.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) T cell receptor ligand;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- b) re-administering to said subject said treated or educated cells.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) T cell receptor ligand;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- c) re-administering to said subject said treated or educated cells;
- and
- d) administering to said subject:
- i) an effective amount of T cell receptor ligand;
- ii) antigen presenting cells;
- iii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- iv) any combination of the above.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject:
- a) an effective amount of T cell receptor ligand;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
A therapeutic composition for the treatment of a disease in a mammalian subject comprising:
- a) T cell receptor ligands;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease;
- or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite, the result of said administration comprising a change in the number or function of regulatory, immune-regulatory or NKT cells.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite, the result of said administration comprising the reduction, inhibition, or decrease of the number or function of regulatory, immune-regulatory or NKT cells.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite, the result of said administration comprising the stimulation or increase of the number or function of regulatory, immune-regulatory or NKT cells.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite and antigen presenting cells, the result of said administration comprising a decrease in regulatory, immune-regulatory or NKT cell proliferation.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite and antigen presenting cells, the result of said administration comprising an increase in regulatory, immune-regulatory or NKT cell proliferation.
An in vitro screening assay for an analogue or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a disease resulting in a change in the number of regulatory, immune-regulatory or NKT cells, said assay comprising:
- a) providing in vitro:
- (i) regulatory, immune-regulatory or NKT cells from said subject or another subject;
- (ii) antigen presenting cells;
- (v) analogue or derivative of said intermediary metabolite;
- b) identifying a decrease in said regulatory, immune-regulatory or NKT cell proliferation.
An in vitro screening assay for an analogue or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a disease resulting in a change in the number of regulatory, immune-regulatory or NKT cells, said assay comprising:
- a) providing in vitro:
- i) regulatory, immune-regulatory or NKT cells and BSA in a first test tube;
- ii) regulatory, immune-regulatory or NKT cells and said analogue or derivative of an intermediary metabolite in a second test tube;
- iii) regulatory, immune-regulatory or NKT cells, antigen presenting cells and BSA in a third test tube;
- iv) regulatory, immune-regulatory or NKT cells, antigen-presenting cells and an analogue or derivative of said intermediary metabolite;
- b) determining the amount of regulatory, immune-regulatory or NKT cell proliferation in each of said tubes;
- and
- c) identifying the least amount of regulatory, immune-regulatory or NKT cell proliferation in said fourth tube.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) intermediary metabolite;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- b) re-administering to said subject said treated or educated cells, the result of said administration comprising a change in the number of said cells.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) intermediary metabolite;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- c) re-administering to said subject said treated or educated cells;
- d) administering to said subject:
- i) an effective amount of an intermediary metabolite;
- ii) antigen presenting cells;
- iii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- iv) any combination of the above;
- e) the result of said administration comprising a change in the number of regulatory cells, immune-regulatory cells or NKT cells.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject:
- a) an effective amount of an intermediary metabolite;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above;
- e) the result of said administration comprising a change in the number of regulatory cells, immune-regulatory cells or NKT cells.
A method for treating a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite so as to modulate or change at least one component in the immune system of said subject.
A therapeutic composition for the treatment of a disease in a mammalian subject, the administration of said composition resulting in a change in the number of regulatory, immune-regulatory or NKT cells, said composition comprising:
- a) an intermediary metabolite;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease;
- or antigens or epitopes associated with the immune-mediated inflammatory response;
- d) any combination of the above.
The use of an intermediary metabolite in the manufacture of a composition for the manipulation of regulatory, immune-regulatory or NKT cells in a mammalian subject suffering from a disease.
The method of claim wherein said change comprises a stimulation or increase in the number or function of said cells.
A method for the treatment of an immune-mediated or immune-related disorder or disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution in said subject.
A method for the treatment of an immune-mediated or immune-related disorder or disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution in said subject and/or a change in the peripheral/intrahepatic T cell ratio.
A method for the treatment of an immune-mediated or immune-related disorder or disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution in said subject and/or a change in intrahepatic CD8+T cell trapping.
A method for the treatment of an immune-mediated or immune regulated disorder or disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite and/or antigen presenting cells, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution.
A method for the treatment of an immune-mediated or immune regulated disorder or disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite and/or antigen presenting cells, the result of said administration comprising an alteration of the function of the regulatory, immune-regulatory or NKT cell distribution.
An in vitro screening assay for an analogue or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a disease- resulting in an alteration of the regulatory, immune-regulatory or NKT cell distribution, said assay comprising:
- a) providing in vitro:
- (i) regulatory, immune-regulatory or NKT cells from said subject or another subject;
- (ii) antigen presenting cells;
- (vi) analogue or derivative of said intermediary metabolite;
- b) identifying a decrease in said regulatory, immune-regulatory and NKT cell proliferation.
An in vitro screening assay for an analogue or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a disease resulting in a change of the regulatory, immune-regulatory or NKT cell distribution, said assay comprising:
- a) providing in vitro:
- i) regulatory, immune-regulatory or NKT cells and BSA in a first test tube;
- ii) regulatory, immune-regulatory or NKT cells and said analogue or derivative of an intermediary metabolite in a second test tube;
- iii) regulatory, immune-regulatory or NKT cells, antigen presenting cells and BSA in a third test tube;
- iv) regulatory, immune-regulatory or NKT cells, antigen-presenting cells and an analogue or derivative of said intermediary metabolite:
- b) determining the amount of regulatory, immune-regulatory or NKT cell proliferation in each of said tubes;
- and
- c) identifying the least amount of regulatory, immune-regulatory or NKT cell proliferation in said fourth tube.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) intermediary metabolite;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- b) re-administering to said subject said treated or educated cells, the result of said administration comprising a change in said cell distribution.
A method for treating a disease in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) intermediary metabolite;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- and
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- c) re-administering to said subject said treated or educated cells;
- d) administering to said subject:
- i) an effective amount of an intermediary metabolite;
- ii) antigen presenting cells;
- iii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- iv) any combination of the above;
- e) the result of said administration comprising a change of the regulatory, immune-regulatory or NKT cell distribution.
A method for the treatment of a disease in a mammalian subject comprising administering to said subject:
- a) an effective amount of an intermediary metabolite;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- of
- d) any combination of the above;
- e) the result of said administration comprising a change of the regulatory, immune-regulatory or NKT cell distribution.
A method for treating a disease in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite so as to modulate or change at least one component in the immune system of said subject.
A therapeutic composition for the treatment of a disease in a mammalian subject, the administration of said composition resulting in a change of the regulatory, immune-regulatory or NKT cell distribution, said composition comprising:
- a) an intermediary metabolite;
- b) antigen presenting cells;
- c) antigens or epitopes associated with said disease;
- or antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
The use of an intermediary metabolite in the manufacture of a composition for the manipulation of regulatory, immune-regulatory or NKT cells in a mammalian subject suffering from an immune-related or immune-mediated disorder or disease.
Dependencies are inferred from the claim text.