Entry inhibitors: Edited by Jose A. EstéCCR5 monoclonal antibodies for HIV-1 therapyOlson, William Ca; Jacobson, Jeffrey MbAuthor Information aProgenics Pharmaceuticals Inc., Tarrytown, New York, USA bDrexel University College of Medicine, Philadelphia, Pennsylvania, USA Correspondence to William C. Olson, PhD, Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA Tel: +1 914 789 2800; e-mail: [email protected] Current Opinion in HIV and AIDS: March 2009 - Volume 4 - Issue 2 - p 104-111 doi: 10.1097/COH.0b013e3283224015 Buy Metrics Abstract Purpose of review To summarize emerging clinical and preclinical data pertaining to the use of CCR5 monoclonal antibodies (mAbs) as therapies for HIV-1 infection. The epitope specificity of CCR5 mAbs is discussed in relation to its critical impact on antiviral activity and CCR5 antagonism. We compare and contrast mAbs and small-molecule CCR5 antagonists in terms of their binding and antiviral properties. Two CCR5 mAbs have entered clinical testing and have successfully completed proof-of-concept studies in HIV-infected individuals, providing initial information on the potential therapeutic utility of these agents. Recent findings New studies support the view that the most potent antiviral CCR5 mAbs recognize the second extracellular loop of CCR5 either exclusively or in combination with the amino terminus. Studies have revealed fundamental differences in how mAbs and small molecules bind CCR5 and inhibit HIV-1. CCR5 mAbs and small-molecule CCR5 antagonists have demonstrated consistent antiviral synergy and limited or no viral cross-resistance in independent studies. Single intravenous infusions of CCR5 mAbs significantly reduced HIV-1 RNA levels in infected individuals for 2–3 weeks without appreciable toxicity. Summary CCR5 mAbs have demonstrated broad and potent antiviral activity in vitro. Clinical studies have established CCR5 mAbs as potent antiretroviral agents with prolonged activity following a single dose. CCR5 mAbs represent both a distinct class of CCR5 inhibitor and a novel approach to HIV-1 therapy. © 2009 Lippincott Williams & Wilkins, Inc.