β-mannosylceramide and stimulation of NKT cell anti-tumor immunity
AssigneesThe United States of America, as represented by the Secretary, Department of Health and Human Services, The University of Birmingham
InventorsJay A. Berzofsky, Jessica J. O'Konek, Masaki Terabe, Petr A. Illarionov, Gurdyal S. Besra
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Abstract
β-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of α-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising β-mannosylceramide, as well as methods of treatment of tumors are also provided.
Claims22
A method for activating a mammalian NKT cell in vitro comprising:
- culturing in vitro a mononuclear cell fraction comprising one or more mammalian NKT cells in the presence of a composition in an amount sufficient to activate a mammalian NKT cell in vitro,
- wherein the composition comprises a β-mannosylceramide (β-ManCer) or salt or solvate thereof in a pharmaceutically acceptable carrier, wherein the β-ManCer consists of a β-mannosyl moiety linked to a ceramide moiety, the ceramide moiety consisting of:
- a) a sphingosine moiety linked to
- b) a fatty acid moiety comprising a linear or branched, saturated or unsaturated, aliphatic hydrocarbon group having from about 8 to about 49 carbon atoms.
A method of inducing an immune response, treating cancer, or inhibiting growth of a tumor in a subject, the method comprising
- administering to the subject a composition in an amount effective to induce an immune response, treat cancer, or inhibit growth of a tumor in the subject,
- wherein the composition comprises a β-mannosylceramide (β-ManCer) or salt or solvate thereof in a pharmaceutically acceptable carrier, wherein the β-ManCer consists of a β-mannosyl moiety linked to a ceramide moiety, the ceramide moiety consisting of:
- a) a sphingosine moiety linked to
- b) a fatty acid moiety comprising a linear or branched, saturated or unsaturated, aliphatic hydrocarbon group having from about 8 to about 49 carbon atoms, and
- wherein the cancer is selected from the group consisting of lung cancer, colon cancer, and skin cancer, and the tumor is selected from the group consisting of a lung tumor, a colon tumor, and a skin tumor.
A method of treating cancer or inhibiting growth of a tumor in a subject, the method comprising
- culturing in vitro a mononuclear cell fraction comprising one or more mammalian NKT cells in the presence of a composition in an amount sufficient to activate a mammalian NKT cell in vitro,
- administering the activated mammalian NKT cells to the subject in an amount effective to treat cancer or inhibit growth of a tumor in the subject,
- wherein the composition comprises a β-mannosylceramide (β-ManCer) or salt or solvate thereof in a pharmaceutically acceptable carrier, wherein the β-ManCer consists of a β-mannosyl moiety linked to a ceramide moiety, the ceramide moiety consisting of:
- a) a sphingosine moiety linked to
- b) a fatty acid moiety comprising a linear or branched, saturated or unsaturated, aliphatic hydrocarbon group having from about 8 to about 49 carbon atoms, and
- wherein the cancer is selected from the group consisting of lung cancer, colon cancer, and skin cancer, and the tumor is selected from the group consisting of a lung tumor, a colon tumor, and a skin tumor.
Dependencies are inferred from the claim text.