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ALPHA-GALACTOSYL CERAMIDE ANALOGS AND THEIR USE AS IMMUNOTHERAPIES
专利权人:
ACADEMIA SINICA
发明人:
WONG, CHI-HUEY,YU, ALICE,CHANG, YA-JEN
申请号:
EP08745801
公开号:
EP2144594A4
申请日:
2008.04.14
申请国别(地区):
EP
年份:
2012
代理人:
摘要:
The present disclosure relates to synthetic alpha-galactosyl ceramide (α-GalCer) analogs, and their use as immunotherapies. In one aspect, a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula (1) wherein, n is 0 to 25 X is selected from O and S R1 is selected from H, CH3, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, phenyl-F, C1-C6 alkyl, or C2-C6 branched alkyl R2 is selected from OH and H R3 is selected from C1-C15 alkyl, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, C1-C6 alkyl, or C2-C6 branched alkyl R4 is selected from OH, OSO3H, OSO3Na, and OSO3K and R5 is selected from CH2OH and CO2H or a pharmaceutically acceptable salt thereof forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte and activating the lymphocyte to produce the cytokine response.Linvention concerne des analogues dalpha-galactosyl céramide (a-GalCer), et leur utilisation en immunothérapies. Dans un aspect, un procédé dactivation dune réponse de cytokine chez un sujet comprend ladministration dune quantité efficace dun composé à un sujet qui sujet a un système immunitaire adaptatif comprenant une population de cellules qui comprend au moins un lymphocyte et au moins une cellule présentant un antigène. Le composé est représenté par la structure de formule (1) dans laquelle n vaut 0 à 25 X est choisi parmi O et S R1 est choisi parmi H, CH3 et un phényle, où le phényle est facultativement substitué par H, OH, OCH3, F, CF3, un phényle, un phényl-F, un alkyle en C1-C6 ou un alkyle ramifié en C2-C6
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