Polyunsaturated fatty acid-bound alpha fetoprotein promotes immune suppression by altering human dendritic cell metabolism
AssigneesThe Regents of the University of California, Parker Institute for Cancer Immunotherapy
InventorsLisa Helene Butterfield, Juraj Adamik, Paul Veness Munson
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Abstract
Depending on the fatty acid bound by alpha fetoprotein (AFP), the protein can have an immunosuppressive effect, allowing for treatment of inflammatory diseases, or a neutral effect, allowing for development of dendritic cell vaccines that express AFP peptides, which have use in treating and preventing tumor AFP-expressing cancers.
Claims21
A pharmaceutical composition comprising (i) alpha fetoprotein (AFP) and (ii) dihomo-gamma-linolenic acid (20:3, n-6), arachidonic acid (20:4), prostaglandin E2 (PGE2), prostaglandin A2 (PGA2), prostacyclin (PGl2), thromboxane A2, leukotriene B4, leukotriene C4, or leukotriene E4.
A method of reducing an inflammatory response in a human in need thereof, the method comprising administering a composition comprising a sufficient amount of alpha fetoprotein (AFP) bound to dihomo-gamma-linolenic acid (20:3, n-6)-, arachidonic acid (20:4)-, prostaglandin E2 (PGE2)-, prostaglandin A2 (PGA2)-, prostacyclin (PGl2)-, thromboxane A2-, leukotriene B4-, leukotriene C4-, or leukotriene E4-bound alpha fetoprotein (AFP) thereby reducing the inflammatory response.
A method of preparing a dendritic cell vaccine, the method comprising,
- culturing dendritic cells in a culture medium comprising palmitic acid-bound tumor alpha fetoprotein (tAFP) under conditions to generate mature dendritic cells expressing tAFP-derived HLA-restricted peptides.
The method of any one of claims 10-12, wherein the culture medium comprises a zinc chelator.
A dendritic cell vaccine comprising mature dendritic cells cultured in the presence of palmitic acid-bound alpha fetoprotein (AFP) in the absence of other polyunsaturated fatty acids, wherein the mature dendritic cells express AFP-derived HLA-restricted peptides.
A method, comprising,
- obtaining a sample from a human having liver cancer;
- and
- measuring the amount of, and identity of, polyunsaturated fatty acids bound to tumor alpha fetoprotein (tAFP) in the sample.
Dependencies are inferred from the claim text.