Cancer
OXY111A, NormOxys' allosteric effector of hemoglobin, increases hemoglobin's oxygen-release capacity under hypoxic conditions, and switches off the hypoxia-inducible factor HIF-1 alpha and therefore down-regulates hypoxia-inducible genes. This action has significant effect on tumor growth.
Weekly intravenous injection of OXY111A to rats with Liver Cancer (LC) shows striking results compared with standard doxorubicin chemotherapy. The follow up of LC evolution by computer assisted tomography imaging revealed a significant anticancer effect of OXY111A, showing striking improvement in long-term survival and even cure of nearly all of the treated animals. OXY111A administration did not result in any meaningful alterations of hematologic parameters and was generally well tolerated and devoid of any significant toxicity at optimal dose and schedule of administration.
OXY111A treatment leads to inhibition of tumor growth, inhibition of the metabolic actions of other hypoxia-inducible target genes on glucose metabolism, inhibition of angiogenesis and of cell proliferation, and results in improved survival. The administration of OXY111A as an allosteric effector of hemoglobin, resulting in increased delivery of oxygen to hypoxic tumor tissues represents a major, new mechanism of cancer therapy.
Micro-CT Imaging Showing Eradication of Liver Cancer in Rats Following Treatment with OXY111A
Representative follow-up of liver tumor evolution using recurrent μCT imaging showing eradication of orthotopically implanted Morris Hepatoma in ACI rats by OXY111A treatment. Livers and tumors (indicated by white arrows in 2D slices) were reconstructed from the corresponding 2D DICOM pictures using a 3D virtual-reality software, allowing visualization of the tumors in transparency within the liver. The volumes of each tumor could be also determined from the number of pixels included in the 3D structures and expressed as a ratio of the initial volume as illustrated in the accompanying graph. Chemotherapy with doxorubicin (750μg/kg at 2-week intervals) induced only a retardation in tumor growth, while OXY111A (500 mg/kg each week) completely inhibited tumor growth within 3 weeks.
Hypoxia (decrease in oxygen tension) in solid tumors is a critical regulator of tumor cell growth and invasion. Hypoxic tumors develop their own blood supply, a process known as tumor angiogenesis, which facilitates metastatic spreading. OXY111A, enhances oxygen release by hemoglobin once taken up by red blood cells, counteracts the effects of hypoxia and inhibits angiogenesis in vitro. We have shown in a mouse experimental model that OXY111A in red blood cells (OXY111A-RBC) reduces lung metastases induced by intravenous injection of mouse melanoma cells.
OXY111A has been shown to reduce angiogenesis and to increase the effect of chemotherapy agents in melanoma. Similar observations have been made with pancreatic cancer in rats and nude mice, and in colon cancer in nude mice.