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Home Drugs Method-for-using-phagocytic-particles-and-ATP-receptors-to-deliver-antigens-to-MHC-class-I-receptors-to-induce-immunity-against-microbial-pathogens-or-tumors-or-to-suppress-immunity

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 Method for using phagocytic particles and ATP receptors to deliver antigens to MHC class I receptors to induce immunity against microbial pathogens or tumors or to suppress immunity

Details
Inventors: Silverstein, Samuel C.; Loike, John D.; DiVirgilio, Francesco;
Assignee: The Trustees of Columbia University in the City of New York (New York, NY)
Primary Examiner: Chan; Christina
Assistant Examiner: VanderVegt; F. Pierre
Attorney, Agent or Firm: White, Esq.; John P., Cooper & Dunham LLP

This invention provides methods of delivering an antigen to an Class I or Class II MHC receptors to induce immunity against the antigen in a subject having a disease. This invention also provides methods of delivering an antigen to an Class II or class I MHC receptor to supress immunity against the antigen in a subject having a disease.

DETAILED DESCRIPTION OF THE INVENTION This invention provides a method of delivering an antigen to an Class I MHC receptor to induce immunity against the antigen in a subject having a disease which comprises: a) filling particles with the antigen and ATP resulting in an antigen- and ATP-filled particles (Ag/ATP-filled particles); b) coating the Ag/ATP-filled particles of step (a) with a ligand for an antigen presenting cell resulting in a ligand-coated Ag/ATP-filled particles; c) incubating the ligand-coated Ag/ATP-filled particles of step (b) with isolated ligand-binding antigen presenting cells (APCs) under conditions permitting the ligand-binding APCs to bind to the ligand-coated Ag/ATP-filled particles and APC phagolysosomes to ingest the ligand-coated Ag/ATP-filled particles to facilitate transfer of the ingested antigen from the phagolysosomes into cytoplasm such that the antigen is delivered to a Class I MHC receptor and is expressed on the surface of the APCs (Ag-APCs); and d) administering the antigen presenting cells (APCs) of step (c) to a subject having the disease so as induce Class I MHC presentation and elicit cytotoxic T-lymphocytes against the antigen, thereby inducing immunity against the antigen.
In an embodiment of the above-described method of delivering an antigen to an Class I MHC receptor to induce immunity against the antigen in a subject having a disease, the particle is a type O red blood cell ghost.
In another embodiment of the method the particle is a liposome.
In an embodiment the ligand is selected from the group consisting of an immunoglobulin (IgG), complement component C3b, complement component C3bi, maleic anhydride, an oxidized lipid, a sugar, and a polyanion.
In a further embodiment the antigen presenting cell is selected from the group consisting of a dendritic cell, a Langerhans cell, a monocyte, a mononuclear phagocyte, a macrophage, a Kupfer cell, a microglial cell, an osteoclast, and a bone marrow-derived leukocyte.
In an embodiment the antigen is a purified antigen



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