Erlizumab
Encyclopedia
Erlizumab, also known as rhuMAb, is a recombinant
humanize
d monoclonal antibody that was an experimental immunosuppressive drug
. Erlizumab was developed by Genentech
under a partnership with Roche to treat heart attack, stroke
, and traumatic shock.
and an LFA-1
integrin. Erlizumab was meant to stop lymphocyte movement into inflamed tissue, thereby reducing tissue damage.
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.
's rovelizumab
(LeukArrest), and two drugs developed by Protein Design Labs (PDL) and Centocor
. 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.
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
humanize
Humanize
Humanize may refer to:*Humanize a 2001 album by the British jazz/funk band Big Boss Man*Humanized antibody, a type of monoclonal antibody...
d monoclonal antibody that was an experimental immunosuppressive drug
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
. Erlizumab was developed by Genentech
Genentech
Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...
under a partnership with Roche to treat heart attack, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, and traumatic shock.
Mechanism of action
The drug works by blocking a growth factor in blood vessels. Specifically, erlizumab targets CD18CD18
Integrin beta-2 is a protein that in humans is encoded by the ITGB2 gene.It is the beta subunit of four different structures:* LFA-1 * Macrophage-1 antigen * Integrin alphaXbeta2...
and an LFA-1
LFA-1
Lymphocyte function-associated antigen 1, also known as LFA-1 is found on all T-cells and also on B-cells, macrophages and neutrophils and is involved in recruitment to the site of infection. It binds to ICAM-1 on antigen-presenting cells and functions as an adhesion molecule. LFA-1 is the first...
integrin. Erlizumab was meant to stop lymphocyte movement into inflamed tissue, thereby reducing tissue damage.
Clinical trials
Genentech started clinical trialClinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
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 IcosICOS
Icos Corporation was the largest biotechnology company in the U.S. state of Washington before it was sold to Eli Lilly and Company in 2007. Co-founded in 1989 by George B. Rathmann, a pioneer in the industry and Chief Executive Officer and co-founder of Amgen, Icos focused on the development of...
's rovelizumab
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 suffering from haemorrhagic shock. The drug is a monoclonal antibody that suppresses white blood cells which...
(LeukArrest), and two drugs developed by Protein Design Labs (PDL) and Centocor
Centocor
Janssen Biotech, Inc., formerly Centocor Biotech, Inc., is a biotechnology company that was founded in Philadelphia in 1979 with an initial goal of developing new diagnostic assays using monoclonal antibody technology....
. 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.