Compositions and methods for localized delivery of cytokines for adoptive cell therapy
AssigneePresident and Fellows of Harvard College
InventorsDavid J. Mooney, Yutong Liu, Hua Wang
Life of this patent
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Abstract
Disclosed herein are compositions and methods for metabolically labeling cells using click chemistry reagents. The compositions and methods disclosed herein provide a specific and efficient means of localizing desired agents, such as anti-tumor cytokines, to a variety of cell types for adoptive cell therapy.
Claims32
A method of preventing or treating a cancer in a subject, of enhancing an immune response against a cancer in a subject, or of delivering a non-toxic level of cytokine to a subject, comprising administering to the subject an adoptive cell therapy, wherein the adoptive cell therapy comprises:
- (i) an immune cell comprising a cell-surface glycoprotein coupled to a first click reagent;
- and
- (ii) a cytokine coupled to a second click reagent,
- wherein the cell-surface glycoprotein is covalently linked to the cytokine through a selective reaction between the first click reagent and the second click reagent,
- thereby preventing or treating the cancer, enhancing an immune response against the cancer or delivering the non-toxic level of cytokine to the subject.
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A method of treating a subject in need thereof with an adoptive cell therapy, comprising:
- (i) contacting an immune cell with an unnatural sugar and/or an unnatural sugar nanoparticle to produce an immune cell comprising a cell-surface glycoprotein coupled to a first click reagent;
- and
- (ii) administering to the subject the immune cell comprising the cell-surface glycoprotein coupled to the first click reagent, and a cytokine coupled to a second click reagent,
- wherein the cell-surface glycoprotein is covalently linked to the cytokine through a selective reaction between the first click reagent and the second click reagent,
- thereby treating a subject in need thereof with an adoptive cell therapy.
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A method of producing an adoptive cell therapy, comprising:
- (i) providing an immune cell comprising a cell-surface glycoprotein;
- (ii) contacting the immune cell with an unnatural azido-sugar and/or an unnatural azido-sugar nanoparticle to metabolically label the cell-surface glycoprotein with a first click reagent;
- and
- (iii) contacting the immune cell with a cytokine coupled to a second click reagent,
- wherein the cell-surface glycoprotein is covalently linked to the cytokine through a selective reaction between the first click reagent and the second click reagent,
- thereby producing the adoptive cell therapy.
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An immune cell comprising:
- (i) a cell-surface glycoprotein coupled to a first click reagent;
- and
- (ii) a cytokine coupled to a second click reagent;
- wherein the cell-surface glycoprotein is covalently linked to the cytokine through a selective reaction between the first click reagent and the second click reagent.
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Dependencies are inferred from the claim text.