Ref: Immunobiology. 2015 Aug;220(8):993-8. doi: 10.1016/j.imbio.2015.04.001. Epub 2015 May 5. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov’t

Authors: Zhang Y, Shao D, Ricklin D, Hilkin BM, Nester CM, Lambris JD, Smith RJ.

Highlights:C3 glomerulopathy (C3G) defines a group of untreatable ultra-rare renal diseases caused by uncontrolled activation of the alternative complement pathway. Nearly half of patients progress to end stage renal failure within 10 years. We hypothesized that by targeting C3 Cp40 would provide an effective treatment for C3G.This study shows that Cp40 prevents complement-mediated lysis of sheep erythrocytes in sera from C3G patients, prevents complement dysregulation in the presence of patient-derived autoantibodies to the C3 and C5 convertases, and prevents complement dysregulation associated with disease-causing genetic mutations.In aggregate, these data suggest that Cp40 may offer a novel and promising therapeutic option to C3G patients as a disease-specific, targeted therapy.

Mol Ther. 2015 Jun;23(6):1066-76. doi: 10.1038/mt.2015.49. Epub 2015 Mar 25. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov’t

Highlights: This study demonstrates that for a prototype of the clinical vaccinia virus based product Pexa-Vec, the neutralizing activity of antibodies elicited by smallpox vaccination, as well as the anamnestic response in hyperimmune virus treated cancer patients, is strictly dependent on the activation of complement.In immunized rats, complement depletion stabilized vaccinia virus in the blood and led to improved delivery to tumors. Complement depletion also enhanced tumor infection when virus was directly injected into tumors in immunized animals. The feasibility and safety of using a complement inhibitor, CP40, in combination with vaccinia virus was tested in cynomolgus macaques.CP40 pretreatment elicited an average 10-fold increase in infectious titer in the blood early after the infusion and prolonged the time during which infectious virus was detectable in the blood of animals with preexisting immunity.