PRO 140 is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. It is being investigated as a potential therapy in the treatment of HIV infection.<http://www.cytodyn.com/news-events/media/cytodyn-announces-acquisition-of-pro-140/ by CytoDyn Inc. The United States Food and Drug Administration has designated PRO 140 for fast-track approval.[1] In February 2008, the drug entered Phase 2 clinical trials.[2]
Development [edit]
PRO 140 is being developed by Cytodyn Inc.. In May 2007, results from the phase I clinical trial of the drug demonstrated "potent, rapid, prolonged, dose-dependent, highly significant antiviral activity" for PRO 140. Participants in the highest dosing group received 5 mg/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.[3] The largest individual HIV RNA reductions ranged up to -2.5 log10 among patients receiving both the 2 and 5 mg/kg doses.[4]
Mechanism of action [edit]
PRO 140 a lab made antibody that functions as an entry inhibitor.[5][6] PRO 140 binds to the CCR5 receptor on the CD4 cells, and interferes with HIV's ability to enter the cell. PRO140 a humanized form of a PA14 antibody, is a chemokine receptor CCR5 monoclonal antibody and can inhibit CCR5 tropic HIV-1 at concentrations that do not antagonize the natural activity of CCR5 in vitro. HIV-1 entry is mediated by the HIV-1 envelope glycoproteins gp120 and gp41. The gp120 will bind CD4 and the CCR5co receptor molecule and this triggers gp41-mediated fusion of the viral and cellular membranes. CCR5 is hence needed for the entry of the virus and this infection of healthy cells. PRO 140 the anti-CCR5 monoclonal antibody can stop HIV from entering the cell and stop viral replication. It prevents the virus-cell binding at a distinct site in the CCR5 co-receptor without interfering with its natural activity. Unlike other entry inhibitors, PRO 140 is a monoclonal antibody. The mechanism of inhibition is competitive rather than allosteric.[7] As such, it must be injected to be effective. However, once inside the body, PRO 140 binds to CCR5 for >60 days,[8] which may allow for dosing as infrequently as every other week.[9][10] Compared to Highly active antiretroviral therapy which has been shown to have treatment -related toxicities for HIV infected patients, PRO140 has no multi drug resistance or toxicities.[7]
See also [edit]
External links [edit]
References [edit]
- ^ Brian Lawler. Progenics' Intriguing Study Results. The Motley Fool. 2 May 2007.
- ^ "Phase 2 clinical trials started on PRO 140". AIDS Patient Care STDS 22 (2): 159–60. February 2008. doi:10.1089/apc.2008.9960. PMID 18273941.
- ^ Derek Thaczuk. ICAAC: Phase 1 study provides `proof of concept` for PRO 140, a monoclonal CCR5 antibody. AIDSmap.com. 21 Sept 2007.
- ^ Liz Highleyman. Monoclonal Antibody CCR5 Inhibitor PRO 140 Produces Long-lasting HIV Suppression in Single-dose Study. 28 Sept 2007. HIVandHepatitis.com
- ^ Biswas P, Tambussi G, Lazzarin A (2007). "Access denied? The status of co-receptor inhibition to counter HIV entry". Expert Opin Pharmacother 8 (7): 923–33. doi:10.1517/14656566.8.7.923. PMID 17472538.
- ^ Pugach P, Ketas TJ, Michael E, Moore JP (August 2008). "Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors". Virology 377 (2): 401–7. doi:10.1016/j.virol.2008.04.032. PMC 2528836. PMID 18519143.
- ^ a b L, Li, Sun T, Yang K, Zhang P, and Jia WQ. "Monoclonal CCR5 Antibody for Treatment of People with HIV Infection (Review)." Cochrane Database of Systematic Reviews 2 (2011): n. pag. Print.
- ^ Progenics Pharmaceuticals' HIV Drug, PRO 140, Receives FDA Fast-Track Designation. Press release, 22 Feb 2006. Progenics Pharmaceuticals.
- ^ PRO 140. Progenics Pharmaceuticals.
- ^ Tim Horn. Single-Dose PRO 140 Has Lasting Effects. 21 Sept 2007. POZ.com.
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Chimeric + humanized
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Human ("-kinu-")
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Humanized ("-kizu-", "-kinzu-")
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