Human monoclonal anti-cytomegalovirus (CMV) antibody (MSL 109): enhancement of in vitro foscarnet- and ganciclovir-induced inhibition of CMV replication.
Human CMV causes a number of diseases that cause considerable morbidity and that can be life-threatening in immunocompromised patients, particularly those with AIDS. Ganciclovir (GCV) and Foscarnet (PFA) are currently the drugs of choice for management of CMV disease. Both are not without side effects and have a relatively narrow margin of safety. In this report the effects of a human IgG1 neutralizing monoclonal antibody MSL-109 (MSL, Sandoz Pharmaceuticals) on CMV replication was examined both alone or in combination with either GCV or PFA. Human embryonic lung fibroblasts were infected with CMV strain AD169 with a multiplicity of infection of 3 plaque forming units/cell for 1 h. Prior to infection the virus was incubated for 30 min at 37 degrees C with serial concentrations of the MSL Ab (0.1-3.0 micrograms/ml). Concentrations of GCV (0.3 to 30 microM) or PFA (50-400 microM) were added to CMV-infected cells that had been either previously incubated with MSL or not. Four days after infection CMV replication was measured by DNA/DNA probe hybridization using the Hybriwix system. MSL in combination with GCV had an additive effect that was observed at concentrations of GCV of 3-10 microM and MSL of 1-10 micrograms/ml. On the other hand, MSL (3-10 micrograms/ml) together with PFA (100-400 microM) produced a synergistic effect on CMV replication. The data suggest that MSL at doses achievable in humans, enhanced GCV- and PFA-induced antiviral effect in a dose-dependent manner and that the combination might be clinically useful in the treatment of CMV disease.
Nokta
M
M
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
Tolpin
M D
MD
Nadler
P I
PI
Pollard
R B
RB
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D004357:Drug Synergism; D017245:Foscarnet / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D014759:Viral Envelope Proteins / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; D017245:Foscarnet; D015774:Ganciclovir