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]
| Monoclonal antibody | |
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| Type | F(ab')2 fragment |
| Source | Humanized (from mouse) |
| Target | CD18 |
| Clinical data | |
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Mechanism of action
editThe 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
editGenentech 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
editMultiple 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
edit- ^ 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 17084981.163-80&rft.date=2007-01&rft_id=info:doi/10.1016/j.bbcan.2006.09.001&rft_id=info:pmid/17084981&rft.aulast=Hehlgans&rft.aufirst=S&rft.au=Haase, M&rft.au=Cordes, N&rfr_id=info:sid/en.wikipedia.org:Erlizumab" class="Z3988">
- ^ 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 190257.817-8&rft.date=2000-08&rft_id=https://api.semanticscholar.org/CorpusID:190257#id-name=S2CID&rft_id=info:pmid/10932141&rft_id=info:doi/10.1038/78412&rft.aulast=Dove&rft.aufirst=A&rfr_id=info:sid/en.wikipedia.org:Erlizumab" class="Z3988">
- ^ "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 11733394.2778-83&rft.date=2001-12&rft_id=info:doi/10.1161/hc4801.100236&rft_id=info:pmid/11733394&rft.aulast=Baran&rft.aufirst=KW&rft.au=Nguyen, M&rft.au=McKendall, GR&rft.au=Lambrew, CT&rft.au=Dykstra, G&rft.au=Palmeri, ST&rft.au=Gibbons, RJ&rft.au=Borzak, S&rft.au=Sobel, BE&rft.au=Gourlay, SG&rft.au=Rundle, AC&rft.au=Gibson, CM&rft.au=Barron, HV&rfr_id=info:sid/en.wikipedia.org:Erlizumab" class="Z3988">