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REMOVAL OF TARGET CELLS BY CIRCULATING VIRUS SPECIFIC CYTOTOXIC T CELLS USING MHC CLASS I COMPRISING COMPLEXES
专利权人:
发明人:
KNOETGEN HENDRIK
申请号:
IN8917/CHENP/2013
公开号:
IN2013CN08917A
申请日:
2013.11.06
申请国别(地区):
IN
年份:
2014
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 ß2 microglobulin and (ii) the extracellular domains a1 a2 and a3 of a class I MHC molecule with a relative frequency of less than 1 % or (i) a virus derived peptide (ii) a ß2 microglobulin and (iii) the extracellular domains a1 a2 and a3 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.
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