Chimeric immunomodulatory compounds and methods of using the same-IV
The invention provides immunomodulatory compounds and methods for immunomodulation of individuals using the immunomodulatory compounds.
1. A method of modulating an immune response in an individual comprising administering to an individual a linear chimeric immunostimulatory compound (CIC) comprising the structure N 1 —S 1 —N 2 —S 2 —N 3 ,
wherein N 1 , N 2 , and N 3 are independently selected nucleic acid moieties, at least one of N 1 , N 2 , and N 3 has the sequence 5′-TCGY-3′, where Y is selected from the group consisting of XCGX, XTCG, XXCG, and CGXX, where each X is an independently selected nucleotide;
wherein S 1 is a non-nucleic acid spacer moiety covalently bound to N 1 and N 2 ; S 2 is a non-nucleic acid spacer moiety covalently bound to N 2 and N 3 ; S 1 and S 2 are the same or different; each of S 1 and S 2 comprises hexaethylene glycol (HEG), triethylene glycol (TEG), propyl, butyl, or hexyl; and
wherein said CIC has at least one immunostimulatory activity selected from the group consisting of (i) the ability to stimulate interferon-gamma (IFN-γ) production by human peripheral blood mononuclear cells or (ii) the ability to stimulate interferon-alpha (IFN-α) production by human peripheral blood mononuclear cells.
2. The method of claim 1 wherein at least one of N 1 and N 3 has a sequence 5′-TCGXCGX-3′.
3. The method of claim 1 wherein at least one of N 1 and N 2 has a sequence 5′-TCGXCGX-3′.
4. The method of claim 1 wherein at least one of N 2 and N 3 has a sequence 5′-[(X) 0-2 ]TCG[(X) 2-4 ]-3′, wherein the first X at the 5′ end of the CIC is an A and each following X is an independently selected nucleotide.
5. The method of claim 1 , wherein said modulation comprises an increase in secretion of interferon-gamma (IFN-γ) or interferon-alpha (IFN-α) production by human peripheral blood mononuclear cells.
6. The method of claim 1 , wherein at least one of S 1 and S 2 is a HEG spacer moiety.
7. The method of claim 6 wherein both S 1 and S 2 are HEG spacer moieties.
8. The method of claim 1 wherein at least one nucleic acid moiety comprises the sequence 5′-TCGCCGG-3′, 5′-TCGGCGC-3′ or 5′-TCGTCGT-3′.
9. The method of claim 1 wherein at least one nucleic acid moiety comprises the sequence 5′-TCGCCGG-3′, 5′-TCGGCGC-3′ or 5′-TCGTCGT-3′.