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]
[edit] 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]
[edit] 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]
[edit] 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 (PDL) 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]
[edit] References
- ^ a b "Genentech Announces Phase II Trial of Experimental Anti-CD18 Antibody Did Not Meet Its Primary Objectives". Business Wire. June 16, 2000. http://findarticles.com/p/articles/mi_m0EIN/is_2000_June_16/ai_62759897. Retrieved January 29, 2009.
- ^ a b Altman, Lawrence (May 30, 2000). "THE DOCTOR'S WORLD; In Search of Surprises as Cures for Cancer". The New York Times. http://query.nytimes.com/gst/fullpage.html?res=9E07E7DD163CF933A05756C0A9669C8B63. Retrieved January 29, 2009.
- ^ Hehlgans, Stephanie; Michael Haasea and Nils Cordes (January 2007). "Signalling via integrins: Implications for cell survival and anticancer strategies". Biochimica et Biophysica Acta (BBA) 1775 (1): 163–80. doi:10.1016/j.bbcan.2006.09.001. PMID 17084981.
- ^ a b c d e f Dove, Alan (2000). "CD18 trials disappoint again". Nature Biotechnology 18 (8): 817–8. doi:10.1038/78412. PMID 10932141.
- ^ "Genentech Reports 1996 Third Quarter Results". Genentech. October 21, 1996. http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=4805. Retrieved January 31, 2009.
- ^ a b Barran, Kenneth; Michel Nguyen; George R. McKendall; Costas T. Lambrew; Gary Dykstra; Sebastian T. Palmeri; Raymond J. Gibbons; Steven Borzak; Burton E. Sobel; Steven G. Gourlay; Amy Chen Rundle; C. Michael Gibson; Hal V. Barron (December 4, 2001). "Double-Blind, Randomized Trial of an Anti-CD18 Antibody in Conjunction With Recombinant Tissue Plasminogen Activator for Acute Myocardial Infarction". Circulation 104 (23): 2778–83. doi:10.1161/hc4801.100236. PMID 11733394.
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Chimeric + humanized
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Human ("-kinu-")
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Humanized ("-kizu-", "-kinzu-")
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