Olson, William C

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William C Olson

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Monoclonal antibodies and small-molecules as distinct subclasses of CCR5-targeted therapies for HIV-1

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Retrovirology
Open AccessOral presentation
Monoclonal antibodies and small-molecules as distinct subclasses of 
CCR5-targeted therapies for HIV-1
William C Olson*
Address: Progenics Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591, USA
* Corresponding author    
The chemokine receptor CCR5 provides a portal of entry
for HIV-1 and serves a target for potential new antiretrovi-
ral therapies. CCR5 monoclonal antibodies (mAb) and
small-molecule CCR5 antagonists potently block HIV-1
entry in vitro, and controlled clinical trials have provided
initial proof-of-concept for this mode of therapy. PRO
140 is a humanized CCR5 mAb that broadly and potently
blocks CCR5-mediated HIV-1 entry in preclinical settings,
and this product has entered phase 1b testing in HIV-
infected individuals. In this study, PRO 140 and small-
molecule CCR5 antagonists in development were com-
pared in terms of patterns of viral resistance, synergistic
interactions, competition for CCR5 binding, and related
properties. In studies that examined forced viral resistance
to CCR5 inhibitors in vitro, we observed limited or no
viral cross-resistance between PRO 140 and small-mole-
cule CCR5 antagonists. Potent antiviral synergy was
observed between PRO 140 and small-molecule CCR5
antagonists in vitro. In contrast, modest synergy or addi-
tive effects were observed between PRO 140 and enfuvir-
tide and between different small-molecule CCR5
antagonists used in combination. Synergy between PRO
140 and small-molecule CCR5 antagonists was explained
in part by their non-reciprocal patterns ofA competition
for CCR5 binding. Additional studies indicate that PRO
140 may act as a competitive CCR5 inhibitor while the
small-molecule CCR5 antagonists act via allosteric mech-
anisms. Collectively, the findings suggest that mAb and
small-molecule CCR5 drugs may provide complementary
HIV-1 treatment subclasses.
from 2006 International Meeting of The Institute of Human Virology
Baltimore, USA. 17–21 November, 2006
Published: 21 December 2006
Retrovirology 2006, 3(Suppl 1):S12 doi:10.1186/1742-4690-3-S1-S12
<supplement> <title> <p>2006 International Meeting of The Institute of Human Virology</p> </title> <note>Meeting abstracts. A single PDF containing all abstracts in this Supplement is available <a href=" http://www.biomedcentral.com/content/files/pdf/1742-4690-3-S1-full.pdf ">here</a></note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-3-S1-info.pdf</url></supplement>
© 2006 Olson; licensee BioMed Central Ltd. 


Olson William C

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Monoclonal antibodies and small-molecules as distinct subclasses of CCR5-targeted therapies for HIV-1

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