Sunol Molecular Corp.

Tissue factor (TF) antagonists targeting the factor VII (FVII) binding domain have been shown to interrupt acute vascular thrombus formation without impairing haemostasis in non-human primates. In this study, we evaluate whether a human/mouse chimeric monoclonal antibody (ALT-836, formerly known as Sunol-cH36) blocking the factor X/factor IX (FX/FIX) binding site of tissue factor could achieve similar clinical benefits in an arterial thrombosis model induced by surgical endarterectomy in chimpanzees. In this model, sequential surgical endarterectomies on right and left superficial femoral arteries were performed 30 days apart in five chimpanzees. A bolus (1 mg/kg) of ALT-836 was injected intravenously immediately preceding the restoration of flow in the endarterectomised femoral artery. Pre-surgical labelling of autologous platelets using (111)In-Oxine and post-surgical gamma camera imaging of (111)In-platelet deposition at endarterectomy sites was performed. The manipulated arterial segments were harvested for patency analysis 30 days following surgery. The results indicate that ALT-836 was highly effective at reducing acute vascular thrombosis, with no significant variations in surgical blood loss and template-bleeding time in the treated group compared to the control animals. These data suggest that ALT-836 is an effective and safe antithrombotic agent in preventing TF-initiated vascular thrombogenesis without compromising haemostasis.

A review and discussion with 14 references Infection with enterohemorrhagic E. coli serotype O157:H7 is the foremost infectious cause of hemolytic-uremic syndrome. There is no established therapy for infection with O157:H7 and the antibiotic treatment is contraindicated. The authors hypothesized that administration of antibodies that could neutralize the toxins produced by O157:H7 and other Shiga toxin-producing E. coli (STEC) strains will be protective. Here, they discuss: construction of chimeric anti-Stx1 and anti-Stx2 antibodies; evaluation of chimeric antibodies by ELISA; in vitro neutralization capacity of the chimeric antibodies; and testing the protective efficacy of the chimeric antibodies in mice.