Confluence regulated adhesion molecules useful in modulating vascular permeability
View Patent ↗The invention relates to new polypeptides in isolated form belonging to a subfamily of the human immunoglobulin superfamily, which polypeptide shows at least 70% sequence homology with the amino acid sequence of the murine Confluency Regulated Adhesion Molecules 1 or 2 (CRAM-1 or CRAM-2) as depicted in FIG. 3 , upper and second row, respectively, and antibodies thereto as well as their use in treatment of inflammation and tumors.
1. An isolated nucleic acid molecule comprising:
a) a polynucleotide sequence encoding SEQ ID NO: 13;
b) a polynucleotide sequence that hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5×SSC and 0.1% SDS and wherein said amino acid sequence increases transendothelial migration of leukocytes;
c) a polynucleotide sequence encoding a polypeptide comprising amino acids 1-291 of SEQ ID NO: 13;
d) a polynucleotide sequence encoding a polypeptide comprising amino acids 1-159 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes;
e) a polynucleotide sequence encoding a polypeptide comprising amino acids 25-241 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes;
f) a polynucleotide sequence encoding a polypeptide comprising amino acids 1-238 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes;
g) a polynucleotide sequence that hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-159 of SEQ ID NO: 13, amino acids 25-241 of SEQ ID NO: 13, or amino acids 1-238 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5×SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes; or
h) a polynucleotide sequence encoding a fusion protein comprising:
i) amino acids 25-241 of SEQ ID NO:13;
ii) amino acids 1-159 of SEQ ID NO: 13; or
iii) amino acids 1-238 of SEQ ID NO: 13;
wherein said fusion protein inhibits transendothelial migration of leukocytes.
2. A transformed host cell comprising a nucleic acid molecule according to claim 1 .
3. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding SEQ ID NO: 13.
4. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence that hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5×SSC and 0.1% SDS and wherein said amino acid sequence increases transendothelial migration of leukocytes.
5. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 1-291 of SEQ ID NO: 13.
6. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 1-159 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes.
7. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 25-241 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes.
8. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 1-238 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes.
9. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence that hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-159 of SEQ ID NO: 13, amino acids 25-241 of SEQ ID NO: 13, or amino acids 1-238 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5×SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
10. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding a fusion protein comprising amino acids 25-241 of SEQ ID NO: 13, wherein said fusion protein inhibits transendothelial migration of leukocytes.
11. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding a fusion protein comprising amino acids 1-159 of SEQ ID NO: 13, wherein said fusion protein inhibits transendothelial migration of leukocytes.
12. The isolated nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule comprises a polynucleotide sequence encoding a fusion protein comprising amino acids 1-238 of SEQ ID NO: 13, wherein said fusion protein inhibits transendothelial migration of leukocytes.
13. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding SEQ ID NO: 13.
14. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence that hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5×SSC and 0.1% SDS and wherein said amino acid sequence increases transendothelial migration of leukocytes.
15. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 1-291 of SEQ ID NO: 13.
16. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 1-159 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes.
17. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 25-241 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes.
18. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding a polypeptide comprising amino acids 1-238 of SEQ ID NO: 13 and wherein said polypeptide inhibits transendothelial migration of leukocytes.
19. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence that hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-159 of SEQ ID NO: 13, amino acids 25-241 of SEQ ID NO: 13, or amino acids 1-238 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5×SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
20. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding a fusion protein comprising amino acids 25-241 of SEQ ID NO: 13, wherein said fusion protein inhibits transendothelial migration of leukocytes.
21. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding a fusion protein comprising amino acids 1-159 of SEQ ID NO: 13, wherein said fusion protein inhibits transendothelial migration of leukocytes.
22. The host cell according to claim 2 , wherein said host cell comprises a polynucleotide sequence encoding a fusion protein comprising amino acids 1-238 of SEQ ID NO: 13, wherein said fusion protein inhibits transendothelial migration of leukocytes.