Df. Smee et al., COMBINATION OF ANTIVIRAL IMMUNOTOXIN AND GANCICLOVIR OR CIDOFOVIR FORTHE TREATMENT OF MURINE CYTOMEGALOVIRUS INFECTIONS, Antiviral research, 32(3), 1996, pp. 165-171
The effects of two anti-murine cytomegalovirus (MCMV) immunotoxins use
d in combination with ganciclovir (GVC) or cidofovir (HPMPC) against M
CMV were determined in vitro and in mice. The inhibitors were added to
cell cultures 24 or 48 h after MCMV adsorption so as to not affect th
e initial infection rate. The immunotoxins (0.63, 1.25 and 2.5 mu g/ml
) combined with GCV (1.25, 2.5 and 5 mu M) or HPMPC (0.03, 0.06 and 0.
12 mu M) caused synergistic inhibition of virus yield in C127I cells a
t most of the combinations tested. No toxic effect on cell growth in c
ulture was observed at these immunotoxin/drug combinations. The effect
s of immunotoxin and GCV treatment were studied further in MCMV-infect
ed severe combined immunodeficient (SCID) mice. Immunotoxin (1 mg/kg p
er day) given by intraperitoneal (i.p.) injection on days 1, 4 and 7 o
f the infection did not extend the mean day to death compared with the
placebo group. Once daily i.p. treatment with GCV (50 mg/kg per day)
for 7 days starting at 24 h after virus inoculation extended survival
time almost 11 days. The combination of immunotoxin plus GCV was bette
r than GCV alone, extending the mean day to death an additional 2 to 3
days, which is suggestive of a synergistic effect.