| Monoclonal antibody | |
|---|---|
| Type | F(ab')2 fragment |
| Source | Humanized (from mouse) |
| Target | CD18 |
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Erlizumab, also known as rhuMAb, is a recombinant humanized 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. [1]
Mechanism of action
The drug works by blocking a growth factor in blood vessels. [2] Specifically, erlizumab targets CD18 and an LFA-1 integrin. [3] Erlizumab was meant to stop lymphocyte movement into inflamed tissue, thereby reducing tissue damage. [4]
Clinical trials
Genentech started clinical trials on the drug in October 1996. [5] During clinical trials, six patients suddenly started coughing up blood, and four of them later died. [2] In June 2000, preliminary phase II clinical trial results showed that erlizumab did not meet Genentech's goals. [1] Genentech's primary goal was for the drug to increase blood flow to the heart within 90 minutes of administering the medicine. [4]
Other anti-CD18 drugs
Multiple companies have tried to develop anti-CD18 drugs, but none of them have been successful. [4] Among them are Icos's rovelizumab (LeukArrest), and two drugs developed by Protein Design Labs and Centocor. [4] Although trials in humans have not gone well, the research of CD18 drugs in animals has been encouraging. [4] It is thought that the experimental medicines are affecting the lymphocyte adhesion pathway in humans in unintended ways. [4] One hypothesis is that the endothelial cell barrier function fails when blood supply is low for a prolonged time in humans. [6] If this is true, the drug is not able to stop lymphocyte movement into inflamed tissue. [6]
References
- ^ a b "Genentech Announces Phase II Trial of Experimental Anti-CD18 Antibody Did Not Meet Its Primary Objectives". Business Wire. June 16, 2000. Retrieved January 29, 2009.
- ^ a b Altman L (May 30, 2000). "THE DOCTOR'S WORLD; In Search of Surprises as Cures for Cancer". The New York Times. Retrieved January 29, 2009.
- ^ Hehlgans S, Haase M, Cordes N (January 2007). "Signalling via integrins: implications for cell survival and anticancer strategies". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1775 (1): 163–80. doi: 10.1016/j.bbcan.2006.09.001. PMID 17084981.
- ^ a b c d e f Dove A (August 2000). "CD18 trials disappoint again". Nature Biotechnology. 18 (8): 817–8. doi: 10.1038/78412. PMID 10932141. S2CID 190257.
- ^ "Genentech Reports 1996 Third Quarter Results". Genentech. October 21, 1996. Retrieved January 31, 2009.
- ^ a b Baran KW, Nguyen M, McKendall GR, Lambrew CT, Dykstra G, Palmeri ST, et al. (December 2001). "Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study". Circulation. 104 (23): 2778–83. doi: 10.1161/hc4801.100236. PMID 11733394.