GLYCOSYLATED SPECIFICITY EXCHANGERS THAT INDUCE AN ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY (ADCC) RESPONSE
The present invention is directed to ligand/receptor and antigen/antibody specificity exchangers comprising a saccharide or glycoconjugate. Methods of making these specificity exchangers and methods of using said specificity exchangers to treat or prevent human disease are described herein.
1 . A method of inducing an antibody dependent cellular cytotoxicity (ADCC) in a subject in need thereof, comprising:
identifying a subject in need of an ADCC response against HIV infected cells, wherein said subject has a CD4 cell count that allow safe induction of an ADCC response against CD4 infected cells;
providing to said identified subject an effective amount of a glycoconjugate peptide comprising a binding fragment of a CD4 receptor for HIV gp120 synthetically conjugated to gal α (1,3) gal P; and
measuring the reduction of HIV viral load in said subject.
2 . The method of claim 1 , wherein said subject is evaluated for presence of natural antibodies specific for gal α (1,3) gal β before administration of said glycoconjugate peptide.
3 . The method of claim 1 , wherein said gal α (1,3) gal β is synthetically conjugated to said binding fragment of a CD4 receptor for HIV gp120 by attachment at one amino acid.
4 . The method of claim 1 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 200 amino acids in length.
5 . The method of claim 1 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 150 amino acids in length.
6 . The method of claim 1 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 100 amino acids in length.
7 . The method of claim 1 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 50 amino acids in length.
8 . The method of claim 1 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 25 amino acids in length.
9 . The method of claim 1 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than or equal to 15 amino acids in length.
10 . The method of claim 1 , wherein said gal α (1,3) gal β is synthetically conjugated to a hydroxylated amino acid.
11 . The method of claim 1 , wherein said gal α (1,3) gal β is synthetically conjugated by an NH 2 -linkage.
12 . The method of claim 1 , wherein said gal α (1,3) gal β is synthetically conjugated to the N-terminal end of said binding fragment of a CD4 receptor for HIV gp120.
13 . The method of claim 3 , wherein said gal α (1,3) gal β is synthetically conjugated to a hydroxylated amino acid.
14 . The method of claim 3 , wherein said gal α (1,3) gal β is synthetically conjugated by an NH 2 -linkage.
15 . The method of claim 3 , wherein said gal α (1,3) gal β is synthetically conjugated to the N-terminal end of said binding fragment of a CD4 receptor for HIV gp120.
16 . The method of claim 1 , wherein said subject is a human.
17 . The method of claim 1 , further comprising measuring ADCC of said infected cells mediated by NK cells.
18 . A method of neutralizing Human Immunodeficiency Virus (HIV) infection comprising:
identifying an HIV infected cell; and
contacting said cell with a glycoconjugate peptide comprising a binding fragment of a CD4 receptor for HIV gp120 synthetically conjugated to gal α (1,3) gal P; and,
measuring neutralization of HIV.
19 . The method of claim 18 , wherein said gal α (1,3) gal p is synthetically conjugated to said binding fragment of a CD4 receptor for HIV gp120 by attachment at one amino acid.
20 . The method of claim 18 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 200 amino acids in length.
21 . The method of claim 18 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 150 amino acids in length.
22 . The method of claim 18 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 100 amino acids in length.
23 . The method of claim 18 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 50 amino acids in length.
24 . The method of claim 18 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 25 amino acids in length.
25 . The method of claim 18 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than or equal to 15 amino acids in length.
26 . The method of claim 18 , wherein said gal α (1,3) gal 13 is synthetically conjugated to a hydroxylated amino acid.
27 . The method of claim 18 , wherein said gal α (1,3) gal β is synthetically conjugated by an NH 2 -linkage.
28 . The method of claim 18 , wherein said gal α (1,3) gal β is synthetically conjugated to the N-terminal end of said binding fragment of a CD4 receptor for HIV gp120.
29 . The method of claim 19 , wherein said gal α (1,3) gal β is synthetically conjugated to a hydroxylated amino acid.
30 . The method of claim 19 , wherein said gal α (1,3) gal β is synthetically conjugated by an NH 2 -linkage.
31 . The method of claim 19 , wherein said gal α (1,3) gal β is synthetically conjugated to the N-terminal end of said binding fragment of a CD4 receptor for HIV gp120.
32 . A method of inducing an antibody dependent cellular cytotoxicity (ADCC) response against an HIV infected cell comprising:
indentifying an HIV infected cell;
contacting said cell with an effective amount of a glycoconjugate peptide comprising a binding fragment of a CD4 receptor for HIV gp120 synthetically conjugated to gal α (1,3) gal β; and
measuring an ADCC response against said HIV infected cell.
33 . The method of claim 32 , wherein said measuring of the ADCC response comprises a measurement of cellular cytotoxicity mediated by NK cells.
34 . The method of claim 32 , wherein said gal α (1,3) gal β is synthetically conjugated to said binding fragment of a CD4 receptor for HIV gp120 by attachment at one amino acid.
35 . The method of claim 32 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 200 amino acids in length.
36 . The method of claim 32 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 150 amino acids in length.
37 . The method of claim 32 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 100 amino acids in length.
38 . The method of claim 32 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 50 amino acids in length.
39 . The method of claim 32 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than 25 amino acids in length.
40 . The method of claim 32 , wherein said binding fragment of a CD4 receptor for HIV gp120 is less than or equal to 15 amino acids in length.
41 . The method of claim 32 , wherein said gal α (1,3) gal β is synthetically conjugated to a hydroxylated amino acid.
42 . The method of claim 32 , wherein said gal α (1,3) gal β is synthetically conjugated by an NH 2 -linkage.
43 . The method of claim 32 , wherein said gal α (1,3) gal β is synthetically conjugated to the N-terminal end of said binding fragment of a CD4 receptor for HIV gp120.
44 . The method of claim 34 , wherein said gal α (1,3) gal β is synthetically conjugated to a hydroxylated amino acid.
45 . The method of claim 34 , wherein said gal α (1,3) gal β is synthetically conjugated by an NH 2 -linkage.
46 . The method of claim 34 , wherein said gal α (1,3) gal β is synthetically conjugated to the N-terminal end of said binding fragment of a CD4 receptor for HIV gp120.
47 . The method of claim 32 , wherein said HIV infected cell is present in a human.