Novel Triggering Receptor Involved in Natural Cytotoxicity Mediated by Human Natural Killer Cells and Antibodies That Identify the Same

Abstract

The invention relates to a novel compound termed NKp30 that is selectively expressed by all mature NK cells and that is involved in human natural cytoxicity as an activatory receptor, to new antibodies that bind to the NKp30 structure, and to the pharmaceutical and medicinal uses thereof.

1 . A composition of matter comprising:
 a) at least one polypeptide that is at least 80% identical over its entire length to a polypeptide selected from SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or an immunogenic fragment of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7;   b) a polypeptide selected from SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or an immunogenic fragment of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7;   c) a least one polynucleotide sequence that is at least 80% identical over its entire length to a polynucleotidic sequence selected from SEQ ID NO: 1, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13;   d) a polynucleotide sequence that encodes the polypeptide of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or an immunogenic fragment of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7;   e) a polynucleotide sequence selected from SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 polynucleotide, or SEQ ID NO: 12 polynucleotide;   f) antibodies that bind to the polypeptide of (a) or (b) or antigen binding fragments of said antibodies;   g) a solid support to which is attached at least one antibody that binds to the polypeptide of (a) or (b);   h) a hybridoma that produces a monoclonal antibody that is directed against at least one polypeptide as set forth in (a) or (b);   i) a bispecific antibody or antigen binding fragment thereof according to claim  22 , and another antibody or binding fragment thereof, which specifically binds to a polypeptide as set forth in (a) or (b);   j) a kit comprising an antibody according to (f); or   k) a kit according to 0) which further comprises an antibody selected from the group consisting of anti-NKp46 antibodies and anti-NKp44 antibodies;   
     
     
         2 . A method for grafting enhancement, GvH inhibition, GvT stimulation, and/or for the prevention, palliation, and/or therapy of a tumor and/or of microorganism infection, comprising the use of a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an antibody that specifically binds to: 1) a polypeptide that is at least 80% identical over its entire length to a polypeptide selected from SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or an immunogenic fragment of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7; or 2) a polypeptide selected from SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or an immunogenic fragment of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7. 
     
     
         3 . A method of using a composition of matter according to  claim 1  for detecting or quantifying the presence of Natural Killer (NK) cells in a biological sample; the selective removal of NK cells from a biological sample; the positive and selective purification NK cells from a biological sample; stimulating NK cell cytotoxicity; grafting a cell, tissue or organ; inhibiting NK cell cytotoxicity or stimulating NK cell cytotoxicity. 
     
     
         4 . The method according to  claim 3 , said method comprising a method for detecting or quantifying the presence of NK cells in a biological sample, comprising:
 contacting the biological sample with composition of matter comprising an antibody according to  claim 1  under conditions appropriate for immune complex formation, and   detecting or quantifying the immune complexes thus formed.   
     
     
         5 . The method according to  claim 3 , said method comprising detecting or quantifying the presence of NK cells in a biological sample, comprising:
 contacting the biological sample with a composition of matter comprising a polynucleotide according to  claim 1  under conditions appropriate for the formation of polynucleotide hybridization products, and   detecting or quantifying the hybridization products thus formed.   
     
     
         6 . The method according to  claim 3 , said method for the selective removal of NK cells from a biological sample comprising:
 contacting the biological sample with a composition of matter comprising an antibody according to  claim 1  and,   removing the immune complexes thus formed.   
     
     
         7 . The method according to  claim 3 , said method for the positive and selective purification NK cells from a biological sample, comprising:
 contacting the biological sample with a composition of matter comprising an antibody according to  claim 1  and   recovering the cells from the immune complexes thus formed.   
     
     
         8 . The method according to  claim 3 , said method for stimulating NK cell cytotoxicity, comprising:
 contacting said NK cells under physiological conditions with a composition of matter comprising an antibody according to  claim 1 .   
     
     
         9 . The method according to  claim 3 , said method for inhibiting NK cell cytotoxicity, comprising:
 contacting said NK cells under physiological conditions with at least one product chosen among the group consisting of the antigen binding fragments of antibodies of  claim 1  and the compounds capable of inhibiting the interactions between NKp30 transmembrane region and CD3ζ.   
     
     
         10 . The method according to  claim 3 , said grafting method comprising contacting an organism chosen among the group consisting of a cell to be grafted, a tissue to be grafted, an organ to be grafted, and the host organism with an antibody composition according to  claim 1 .