Apo-2 receptor

Abstract

Novel polypeptides, designated Apo-2, which are capable of modulating apoptosis are provided. Compositions including Apo-2 chimeras, nucleic acid encoding Apo-2, and antibodies to Apo-2 are also provided.

What is claimed is:  
     
         1 . Isolated Apo-2 polypeptide having at least 80% amino acid sequence identity with native sequence Apo-2 polypeptide comprising amino acid residues 1 to 411 of SEQ ID NO:1.  
     
     
         2 . The Apo-2 polypeptide of  claim 1  wherein said polypeptide has at least 90% amino acid sequence identity.  
     
     
         3 . The Apo-2 polypeptide of  claim 2  wherein said polypeptide has at least 95% amino acid sequence identity.  
     
     
         4 . Isolated Apo-2 polypeptide comprising amino acid residues 1 to 411 of SEQ ID NO:1.  
     
     
         5 . Isolated extracellular domain sequence of Apo-2 polypeptide comprising amino acid residues 54 to 182 of SEQ ID NO:1.  
     
     
         6 . The extracellular domain sequence of  claim 5  comprising amino acid residues 1 to 182 of SEQ ID NO:1.  
     
     
         7 . Isolated death domain sequence of Apo-2 polypeptide comprising amino acid residues 324 to 391 of SEQ ID NO:1.  
     
     
         8 . A chimeric molecule comprising the Apo-2 polypeptide of  claim 1  or the extracellular domain sequence of  claim 5  fused to a heterologous amino acid sequence.  
     
     
         9 . The chimeric molecule of  claim 8  wherein said heterologous amino acid sequence is an epitope tag sequence.  
     
     
         10 . The chimeric molecule of  claim 8  wherein said heterologous amino acid sequence is an immunoglobulin sequence.  
     
     
         11 . The chimeric molecule of  claim 10  wherein said immunoglobulin sequence is an IgG.  
     
     
         12 . Isolated nucleic acid comprising a DNA encoding the polypeptide of  claim 1 , the extracellular domain sequence of  claim 5 , or the death domain sequence of  claim 7 .  
     
     
         13 . The nucleic acid of  claim 12  wherein said DNA encodes an Apo-2 polypeptide comprising amino acid residues 1 to 411 of SEQ ID NO:1.  
     
     
         14 . A vector comprising the nucleic acid of  claim 12 .  
     
     
         15 . The vector of  claim 14  operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         16 . The vector of  claim 14  comprising ATCC deposit accession number 209021.  
     
     
         17 . A host cell comprising the vector of  claim 14 .  
     
     
         18 . The host cell of  claim 17  comprising a CHO cell.  
     
     
         19 . The host cell of  claim 17  comprising  E. coli.    
     
     
         20 . The host cell of  claim 17  comprising a yeast cell.  
     
     
         21 . A process of producing an Apo-2 polypeptide comprising culturing the host cell of  claim 17  under conditions sufficient to express Apo-2 polypeptide and recovering the expressed Apo-2 polypeptide from the culture.  
     
     
         22 . An Apo-2 polypeptide which is obtained or obtainable by expressing the polypeptide encoded by the cDNA insert in ATCC deposit accession number 209021.  
     
     
         23 . A non-human, transgenic animal which contains cells that express DNA encoding Apo-2 polypeptide.  
     
     
         24 . The animal of  claim 23  which is a mouse or rat.  
     
     
         25 . A non-human, knockout animal which contains cells having an altered gene encoding Apo-2 polypeptide.  
     
     
         26 . The animal of  claim 25  which is a mouse or rat.  
     
     
         27 . An antibody which specifically binds to an Apo-2 polypeptide.  
     
     
         28 . The antibody of  claim 27  which is a monoclonal antibody.  
     
     
         29 . The antibody of  claim 27  comprising an agonistic antibody.  
     
     
         30 . The antibody of  claim 27  comprising a blocking antibody.  
     
     
         31 . The antibody of  claim 24  comprising a chimeric antibody.  
     
     
         32 . The antibody of  claim 28  wherein said antibody is an IgG antibody.  
     
     
         33 . The antibody of  claim 28  wherein said antibody comprises an Fab fragment.  
     
     
         34 . The antibody of  claim 28  wherein said antibody comprises a scFv fragment.  
     
     
         35 . The antibody of  claim 28  wherein said antibody comprises a F(ab′)2 fragment.  
     
     
         36 . The antibody of  claim 27  wherein said antibody comprises a human antibody.  
     
     
         37 . The antibody of  claim 28  having the biological characteristics of the monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number HB-12456.  
     
     
         38 . The antibody of  claim 28  wherein the antibody binds to the same epitope as the epitope to which the monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number HB-12456 binds.  
     
     
         39 . A hybridoma cell line which produces the antibody of  claim 28 .  
     
     
         40 . The hybridoma cell line deposited as ATCC accession number HB-12456.  
     
     
         41 . The monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number HB-12456.  
     
     
         42 . The antibody of  claim 27  wherein said antibody is a single-chain antibody.  
     
     
         43 . The antibody of  claim 42  wherein said antibody comprises the 16E2 antibody.  
     
     
         44 . The antibody of  claim 42  wherein said antibody comprises the 20E6 antibody.  
     
     
         45 . The antibody of  claim 42  wherein said antibody comprises the 24C4 antibody.  
     
     
         46 . The antibody of  claim 42  wherein said antibody is fused to an epitope tag sequence.  
     
     
         47 . A chimeric molecule comprising the antibody of  claim 27  fused to a heterologous amino acid sequence.  
     
     
         48 . The chimeric molecule of  claim 47  wherein said heterologous amino acid sequence comprises an immunoglobulin sequence.  
     
     
         49 . A dimeric molecule comprising the Apo-2 antibody of  claim 27  and a heterologous antibody.  
     
     
         50 . A homodimeric molecule comprising a first Apo-2 antibody and a second Apo-2 antibody.  
     
     
         51 . Isolated nucleic acid comprising DNA encoding the Apo-2 antibody of  claim 43 .  
     
     
         52 . Isolated nucleic acid comprising DNA encoding the antibody of  claim 44 .  
     
     
         53 . Isolated nucleic acid comprising DNA encoding the antibody of  claim 45 .  
     
     
         54 . A vector comprising the nucleic acid of  claim 51 ,  52 , or  53 .  
     
     
         55 . A host cell comprising the vector of  claim 54 .  
     
     
         56 . A method of producing an Apo-2 antibody comprising culturing the host cell of  claim 55  under conditions wherein the DNA is expressed.  
     
     
         57 . A composition comprising the antibody of  claim 27  and a carrier.  
     
     
         58 . The composition of  claim 57  wherein said carrier is a pharmaceutically-acceptable carrier.  
     
     
         59 . A method of inducing apoptosis in mammalian cancer cells comprising exposing mammalian cancer cells to an effective amount of the Apo-2 agonistic antibody of  claim 29 .  
     
     
         60 . The method of  claim 59  wherein said agonistic antibody comprises a single-chain antibody.  
     
     
         61 . A method of treating mammalian cancer cells comprising exposing mammalian cancer cells to an agent which activates Apo-2.  
     
     
         62 . The method of  claim 61  wherein said agent comprises an agonistic Apo-2 antibody.  
     
     
         63 . An article of manufacture comprising a container and a composition contained within said container, wherein the composition includes Apo-2 polypeptide or Apo-2 antibody.  
     
     
         64 . The article of manufacture of  claim 63  further comprising instructions for using the Apo-2 polypeptide or Apo-2 antibody in vivo or ex vivo.