Erlizumab, also known as rhuMAb, is a recombinant humanized monoclonal antibody that was an experimental

immunosuppressive drug Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...

. Erlizumab was developed by

Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within R ...

under a partnership with

Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX S ...

to treat

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

, and

traumatic shock Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thi ...

Mechanism of action

The drug works by blocking a growth factor in blood vessels. Specifically, erlizumab targets

CD18 In molecular biology, CD18 (Integrin beta chain-2) is an integrin beta chain protein that is encoded by the ''ITGB2'' gene in humans. Upon binding with one of a number of alpha chains, CD18 is capable of forming multiple heterodimers, which play ...

and an

LFA-1 Lymphocyte function-associated antigen 1 (LFA-1) is an integrin found on lymphocytes and other leukocytes. LFA-1 plays a key role in emigration, which is the process by which leukocytes leave the bloodstream to enter the tissues. LFA-1 also mediates ...

integrin. Erlizumab was meant to stop lymphocyte movement into inflamed tissue, thereby reducing tissue damage.

Clinical trials

Genentech started

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s on the drug in October 1996. During clinical trials, six patients suddenly started coughing up blood, and four of them later died. In June 2000, preliminary phase II clinical trial results showed that erlizumab did not meet Genentech's goals. Genentech's primary goal was for the drug to increase blood flow to the heart within 90 minutes of administering the medicine.

Other anti-CD18 drugs

Multiple companies have tried to develop anti-CD18 drugs, but none of them have been successful. Among them are

Icos Icos Corporation (trademark ICOS) was an American biotechnology company and the largest biotechnology company in the U.S. state of Washington, before it was sold to Eli Lilly and Company in 2007. It was founded in 1989 by David Blech, Isaac B ...

rovelizumab Rovelizumab, also known as LeukArrest and Hu23F2G, is a humanized monoclonal antibody which was an experimental immunosuppressive drug. Rovelizumab was developed by Icos to treat patients with haemorrhagic shock. The drug is a monoclonal antibody ...

(LeukArrest), and two drugs developed by Protein Design Labs and

Centocor Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American ...

. Although trials in humans have not gone well, the research of CD18 drugs in animals has been encouraging. It is thought that the experimental medicines are affecting the lymphocyte adhesion pathway in humans in unintended ways. One hypothesis is that the endothelial cell barrier function fails when blood supply is low for a prolonged time in humans. If this is true, the drug is not able to stop lymphocyte movement into inflamed tissue.

References

{{Monoclonals for immune system Monoclonal antibodies Abandoned drugs