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July 7, 2006
Anti-CD4 Antibody Synergistic With Enfuvirtide Against HIV-1 (Reuters Health)
by Will Boggs, MD
Friday July 7, 2006 (Reuters Health) - The humanized monoclonal anti-CD4 antibody TNX-355 is synergistic with the fusion inhibitor enfuvirtide (T-20) in blocking HIV-1 entry into target cells in vitro, according to a report in the June issue of Antimicrobial Agents and Chemotherapy.
"HIV entry is a multi-step process and offers several opportunities for using combinations of agents directed at different steps in this process," Dr. Robert T. Schooley from the University of California, San Diego, told Reuters Health.
Dr. Schooley and colleagues investigated the antiretroviral activity in vitro of TNX-355 and enfuvirtide against several HIV-1 strains.
The 50% inhibitory concentration of TNX-355 alone ranged from 0.13 to 2.0 micrograms/mL when the antibody was present for the initial 18 hours of the culture period, the authors report. Activity was significantly higher when antibody was replenished throughout the culture period.
As noted, TNX-355 also demonstrated significant synergistic antiretroviral activity with enfuvirtide in each experiment. "That this monoclonal antibody acts synergistically with an agent acting at a distal step in the entry cascade supports the antiviral strategy of combining agents directed at sequential steps of the viral entry process," the researchers conclude.
"As chemokine receptor antagonists enter clinical development, three-way antiretroviral synergy efforts directed at the viral entry process should also be examined," they suggest.
"The drug is entering phase III studies in which it will be combined with optimized background antiretroviral therapy to evaluate its utility in multiple combination regimens in vivo," Dr. Schooley added.
