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PRO 140

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.^[1]

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The United States Food and Drug Administration has designated PRO 140 for fast-track approval.^[2]

Development

PRO 140 is being developed by Progenics Pharmaceuticals. In May 2007, they announced results from the phase I clinical 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 a 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

PRO 140 functions as an entry inhibitor.^[5] PRO 140 binds to the CCR5 receptor, and interferes with HIV's ability to enter the cell. Unlike other entry inhibitors, PRO 140 is an monoclonal antibody. As such, it must be injected to be effective. However, once inside the body, PRO 140 binds to to CCR5 for >60 days,^[1] which may allow for dosing as infrequently as every other week.^[6]^[7]

References

^ ^a ^b Progenics Pharmaceuticals' HIV Drug, PRO 140, Receives FDA Fast-Track Designation. Press release, 22 Feb 2006. Progenics Pharmaceuticals.
^ Brian Lawler. Progenics' Intriguing Study Results. The Motley Fool. 2 May 2007.
^ 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.
^ PRO 140. Progenics Pharmaceuticals.
^ Tim Horn. Single-Dose PRO 140 Has Lasting Effects. 21 Sept 2007. POZ.com.

v • d • e Antivirals used against HIV (HAART) (primarily J05)
Nucleoside & Nucleotide Reverse Transcriptase Inbitors (NRTI)	Abacavir (ABC) • Didanosine • Emtricitabine° • Lamivudine (3TC)° • Stavudine • Zidovudine (AZT)° • Tenofovir° • Apricitabine^† • Stampidine^† • Elvucitabine^† • Racivir^† • Zalcitabine^‡
Non-Nucleoside Reverse Transcriptase Inhibitiors (NNRTI)	Efavirenz° • Nevirapine • Etravirine^† • Rilpivirine^† • Loviride^‡ • Delavirdine^‡
Protease Inhibitors (PI)	Atazanavir • Darunavir • Fosamprenavir • Lopinavir° • Nelfinavir • Ritonavir • Saquinavir • Tipranavir • Amprenavir^‡ • Indinavir^‡
Entry/fusion inhibitors	Enfuvirtide • Maraviroc • Vicriviroc^† • PRO 140^†
Integrase inhibitors	Raltegravir • Elvitegravir^†
Maturation inhibitors	Bevirimat^† • Vivecon™^†
Combined formulations	Combivir • Atripla • Trizivir • Truvada • Kaletra • Epzicom
Other & experimental agents	Foscarnet • Synergistic enhancers • Epigallocatechin gallate • Portmanteau inhibitors • Globoidnan A • Griffithsin • Diarylpyrimidines • Calanolide A
^†Undergoing clinical trials, not FDA approved. ^‡Formerly or rarely used agent. °Preferred first-line agent.

v • d • e Humanized monoclonal antibodies
Cancer	Alemtuzumab, Apolizumab, Bevacizumab, Bivatuzumab mertansine, Cantuzumab mertansine, Dacetuzumab, Etaracizumab, Etaratuzumab, Gemtuzumab ozogamicin, Inotuzumab ozogamicin, Labetuzumab, Lintuzumab, Matuzumab, Nimotuzumab, Pertuzumab, Sibrotuzumab, Sontuzumab, Tacatuzumab tetraxetan, Trastuzumab
Immunosuppression	Aselizumab, Atlizumab, Cedelizumab, Daclizumab, Efalizumab, Epratuzumab, Erlizumab, Fontolizumab, Ibalizumab, Lebrilizumab, Mepolizumab, Pascolizumab, Pexelizumab, Reslizumab, Rovelizumab, Ruplizumab, Siplizumab, Talizumab, Teplizumab, Tocilizumab, Toralizumab, Visilizumab
Viral infections	Felvizumab, Palivizumab, PRO 140
other	Bapineuzumab, Certolizumab pegol, Eculizumab, Motavizumab, Natalizumab, Ocrelizumab, Omalizumab, Ranibizumab, Tadocizumab, Tefibazumab, Tucotuzumab celmoleukin, Urtoxazumab

Category: Monoclonal antibodies

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "PRO_140". A list of authors is available in Wikipedia.