See also Complement Receptors under Immunology
CR2 Fusion Constructs
CR2-FH fusion proteins:
Gilkeson (US 7759304; US2008/0221011A1) and WO2007/149567A2) discloses a CR2-FH fusion construct which can be used to treat diseases in which the alternative complement pathway is implicated.
Huang (J. Immunology, 2008, 181: 8068-8076) discloses AP specific inhibitors consisting of a single or dimeric N terminal region of mouse factor H (fH; short consensus repeats 1-5) linked to a CR2 fragment. Both CR2-fH and CR2-fHfH were highly effecting at inhibiting the AP in vitor and demonstrated a higher specific activity than CR2-Crry. Target binindg and complement inhibitory activity of CR2-fH/Cr2-fHfH was depending on CR2 and C3 medaited interactions. CR2-fH and CR2-fHfH provided complete protection from local (intestin) and remote (lung) injury.
Tomlinson (WO2004/045520) discloses complement inhibitors linked to CR2 which can be used for pathologic conditions associated with complement activation. Tomlinson, (US Patent Application 13/380477, published as US 2012/0171206) also teaches Targeted delivery of complement inhibitors to sites of complement activation and diease can improve their efficacy. In one embodiment, the complement inhibitor is a CR2-factor H molcule where the CR2 portion comprises at least the first two N terminal short consensus repeat (SCR) domains of human CR2 and the FH protion comprises at least the first four N terminal SCR domains of human FH. Tomlinson (US 2005/0265995) also discloses antigen specific targetting of complement inhitors to the proximal tubular epithelium.
CR2 – DAF or CD59:
The avidity of CR2 for clustered C3d makes it an effective method of targeting molecules to sites of complement activation. This has been demonstrated by the use of a monovalent CR2 chimera in which CR2 was conjugated with decay acceleration factor (Song, J Clin Invest. 111, 1875-1885, 2003). Song (J. Clinical Invest., 111(12) (2003)) discloses human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the DAF or CD59.
Thurmans discloses that mice injected with CR2 targeted factor H showed attenuation of tubulointerstitial complement activation after renal I/R and ameliorated renal injury (US 13/120125).
CR2-antibody: In addition to its potential as a targetting molecule, CR2-Ig can block c3d-CR2 interactions and has been shown to block primary immune responses in vivo (Hebell, “Supression of the immune response by a soluble complement receptor of B lympocytes. Science, 254, 102-105). Chimaeric antibodies such as CR2-Ig are important in biotechnology through their ability to double the effective concentration of a protein ligand binding site, and to couple this with antibody effector function (Gilbert, J. Mol. Biol. 2006, 356, 397-412).
CR2-SPIO nanoparticle: See SPIO right hand panel