- PRO 140
PRO 140 is a humanized
monoclonal antibody targeted against theCCR5 receptor found onT lymphocytes of the humanimmune system . It is being investigated as a potential therapy in the treatment ofHIV infection . [http://www.natap.org/2006/HIV/022406_02.htm "Progenics Pharmaceuticals' HIV Drug, PRO 140, Receives FDA Fast-Track Designation"] . Press release, 22 Feb 2006. Progenics Pharmaceuticals.]The United States
Food and Drug Administration has designated PRO 140 for fast-track approval. [Brian Lawler. [http://www.fool.com/investing/high-growth/2007/05/02/progenics-intriguing-study-results.aspx "Progenics' Intriguing Study Results"] . The Motley Fool. 2 May 2007.] In February 2008, the drug entered Phase 2 clinical trials.cite journal |author= |title=Phase 2 clinical trials started on PRO 140 |journal=AIDS Patient Care STDS |volume=22 |issue=2 |pages=159–60 |year=2008 |month=February |pmid=18273941 |doi= |url=]Development
PRO 140 is being developed by
Progenics Pharmaceuticals . In May 2007, they announced results from the phase Iclinical trial of the drug. The researchers said the results demonstrated "potent, rapid, prolonged, dose-dependent, highly significant antiviral activity" for PRO 140. Participants in the highest dosing group received 5mg/kg and showed an average viral load decrease of -1.83 log10. On average, reductions of greater than -1 log10 copies/ml were maintained for between two and three weeks, from only a single dose of the drug. [Derek Thaczuk. [http://www.aidsmap.com/en/news/156B61D2-3433-4DD1-A334-CEFF40877DCF.asp "ICAAC: Phase 1 study provides `proof of concept` for PRO 140, a monoclonal CCR5 antibody"] . AIDSmap.com. 21 Sept 2007.] The largest individual HIV RNA reductions ranged up to -2.5 log10 among patients receiving both the 2 and 5 mg/kg doses. [Liz Highleyman. [http://www.hivandhepatitis.com/2007icr/icaac/docs/092807_a.html "Monoclonal Antibody CCR5 Inhibitor PRO 140 Produces Long-lasting HIV Suppression in Single-dose Study"] . 28 Sept 2007. HIVandHepatitis.com]Mechanism of Action
PRO 140 functions as an
entry inhibitor .cite journal |author=Biswas P, Tambussi G, Lazzarin A |title=Access denied? The status of co-receptor inhibition to counter HIV entry |journal=Expert Opin Pharmacother |volume=8 |issue=7 |pages=923–33 |year=2007 |pmid=17472538 |doi=10.1517/14656566.8.7.923 |url=http://www.expertopin.com/doi/abs/10.1517/14656566.8.7.923] cite journal |author=Pugach P, Ketas TJ, Michael E, Moore JP |title=Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors |journal=Virology |volume=377 |issue=2 |pages=401–7 |year=2008 |month=August |pmid=18519143 |doi=10.1016/j.virol.2008.04.032 |url=http://linkinghub.elsevier.com/retrieve/pii/S0042-6822(08)00272-9] PRO 140 binds to the CCR5 receptor, and interferes with HIV's ability to enter the cell. Unlike other entry inhibitors, PRO 140 is a monoclonal antibody. As such, it must be injected to be effective. However, once inside the body, PRO 140 binds to CCR5 for >60 days, [http://www.natap.org/2006/HIV/022406_02.htm "Progenics Pharmaceuticals' HIV Drug, PRO 140, Receives FDA Fast-Track Designation"] . Press release, 22 Feb 2006. Progenics Pharmaceuticals.] which may allow for dosing as infrequently as every other week. [ [http://www.progenics.com/prod_pro140.cfm "PRO 140"] . Progenics Pharmaceuticals.] [Tim Horn. [http://www.poz.com/articles/761_13079.shtml "Single-Dose PRO 140 Has Lasting Effects."] 21 Sept 2007. POZ.com.]External links
[http://ir.progenics.com/common/download/download.cfm?companyid=PGNX&fileid=69481&filekey=f1b9747c-0555-439c-a53e-ec81cf8552eb&filename=PRO140_03.wmv Animation of PRO 140 mechanism]
References
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