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使用包含第一型MHC之複合體透過循環病毒特異性毒殺T細胞以移除標的細胞之方法
专利权人:
F. HOFFMANN-LA ROCHE AG
发明人:
KNOETGEN, HENDRIK,诺珍 韩德克,諾珍 韓德克,诺珍 韩德克,諾珍 韓德克
申请号:
TW101122112
公开号:
TW201311893A
申请日:
2012.06.20
申请国别(地区):
TW
年份:
2013
代理人:
摘要:
Herein is reported a complex comprising as first part an antibody derived part that specifically binds to a target antigen, and as second part a virus-derived peptide linked to a MHC class I protein complex. With the complex as reported herein existing virus-specific circulating cytotoxic T-cells (T-memory-cells or T-effector-cells) of an individual can be directed to cells expressing the target antigen, to which the antibody derived part of the covalent complex specifically binds to, by dressing these cells with a MHC class I complexes mimicking an acute viral infection. Thus, one aspect as reported herein is a complex, characterized in that it comprises one fusion polypeptide that comprises in N- to C-terminal direction either (i) a β2-microglobulin, and (ii) the extracellular domains α1, α2, and α3 of a class I MHC molecule with a relative frequency of less than 1 %, or (i) a virus-derived peptide, (ii) a β2-microglobulin, and (iii) the extracellular domains α1, α2, and α3 of a class I MHC molecule with a relative frequency of 1 % or more, and two polypeptide chains, which are linked by one or more disulfide bonds, wherein the first disulfide-linked polypeptide chain comprises in N- to C-terminal direction (i) an immunoglobulin light or heavy chain variable domain, (ii) an immunoglobulin light or heavy chain constant domain, and (iii) an antibody heavy chain hinge region polypeptide, and the second disulfide-linked polypeptide chain comprises an antibody heavy chain hinge region polypeptide, wherein the fusion polypeptide is either covalently bound either to the C-terminus or the N-terminus of one of the disulfide-linked polypeptide chains, or covalently bound to the N-terminus of an antibody variable domain that is the complementary heavy or light chain variable domain to that comprised in the first disulfide-linked polypeptide chain.本發明係揭示一種複合體,其包含可特異性結合至標的抗原之抗體衍生部分作為第一部分,及病毒衍生肽連接至第一型MHC蛋白質複合體作為第二部分。由於本發明所揭示複合體之存在,藉由使表現標的抗原之細胞帶有第一型MHC複合體以模擬急性病毒感染,可引導個體之病毒特異性循
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中国工程科技知识中心
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