Bavituximab (PGN401) is a human-mouse chimeric

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

against

phosphatidylserine Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via ap ...

, which is a component of cell membranes that is exposed when a cell is transformed into

solid tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

cancer cell or dies, and when cells are infected with

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

. The process of cell death is highly controlled and so there usually no immune response to phosphatidylserine but when bavituximab binds to it, the conjugate appears to stimulate an immune response in humans.

Biology

Phosphatidylserine is the most abundant anionic phospholipid in the cell's plasma membrane, and is usually positioned internally. However, during apoptosis and several pathological conditions including tumorigenesis or infection by some types of viruses, phosphatidylserine is flipped from an internal to an external position. When external, it can potentially be recognized by antibodies. As such, targeting external phosphatidylserine may be a strategy for novel broad-spectrum anti-viral therapies. Bavituximab is an antibody that binds to complexes of the phosphatidylserine-binding plasma protein β2-glycoprotein 1 and anionic phospholipids. In laboratory experiments, treatment with bavituximab was found to rescue mice from otherwise lethal infections of mouse cytomegalovirus (CMV), and Pichinde virus, a model of

Lassa fever virus ''Lassa mammarenavirus'' (LASV) is an arenavirus that causes Lassa hemorrhagic fever, a type of viral hemorrhagic fever (VHF), in humans and other primates. ''Lassa mammarenavirus'' is an emerging virus and a select agent, requiring Biosafety ...

. Proposed mechanisms for this therapeutic effect included bavituximab directly clearing infectious virus from the bloodstream, and the induction of antibody-dependent cellular cytotoxicity of virus-infected cells. Bavituximab inhibited replication of

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...

in preliminary experiments in chicken eggs.

History

Bavituximab was invented at University of Texas Southwestern Medical Center at Dallas; Peregrine Pharmaceuticals exclusively licensed intellectual property related to bavituximab from the university, including US patent 6,300,308 invented by Alan J. Schroit and US Patents 6,406,693 and 6,312,694 invented in the laboratory Philip E. Thorpe.Peregrine press release: Peregrine Pharmaceuticals Licenses Additional Intellectual Property for Its Anti-Phospholipid Therapy Platform Technology
. July 6, 2004 As of January 2016, bavituximab had been in a Phase III clinical trial for

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...

(NSCLC), a Phase II/III trial for breast cancer, a Phase II trial for pancreatic cancer, a phase I/II trial for

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

, and Phase I clinical trials in malignant melanoma and rectal cancer; its development had been discontinued for influenza and prostate cancer.Staff, Adis Insight
Bavituximab profile
Last updated Jan 27 2016 As of 2011 it had been in a Phase II trial for

but no results had been reported as of 2016. The phase III (SUNRISE) trial for NSCLC was discontinued in early 2016 after analysis of interim results. Peregrine changed its business focus to contract manufacturing and changed its name to Avid Bioservices at the end of 2017, and in February 2018 it sold bavituximab and its other drug assets to Oncologie Inc.

References

{{Monoclonals for tumors Monoclonal antibodies for tumors Experimental cancer drugs