Background. Cyclosporin was used in an attempt to suppress the formation of human antimouse antibody (HAMA) after administration of murine monoclonal antibodies.
Methods. Thirteen patients were given oral cyclosporin (8.6–15 mg/kg/day) starting 2 days before administration of technetium‐99m (99mTc) labeled F(ab́)2 (3patients) or Fab (10 patients) murine antibody fragment. Six to nine days later, patients received either rhenium‐186 (186Re)‐labeled F(ab́)2 or an intact antibody. Cyclosporin was continued for 14 days after the second antibody administration.
Results. Five patients (38%) did not develop elevated HAMA titers for up to 8 weeks after antibody administration. These five patients had a median cyclosporin concentration of 726 ng/ml, while the eight patients who developed HAMA had a median cyclosporin level of 364 ng/ml. In contrast, when not given cyclosporin, 86% (24/28) of patients developed HAMA after receiving two doses of F(ab́)2, and 100% (15/15) developed HAMA after receiving Fab followed by intact antibody. Toxicity from cyclosporin included elevation concentrations of bilirubin and creatinine, and increased blood pressure, which rapidly resolved after the cyclosporin was discontinued.
Conclusions. This study demonstrates that cyclosporin given from 2 days before until 2 weeks after administration of either a F(ab́)2 or intact murine antibody can suppress HAMA formation. This strategy may permit administration of repeated doses of murine‐antibody‐based radioimmunotherapy. Cancer 1994; 73:1093–7.
Enterovirus 71 (EV71) can cause brain encephalitis and mortality. However, effective vaccines or chemotherapeutic agents are not yet available. We tested the hypothesis that Pueraria lobata could inhibit the cytotoxic effect of EV71 in a human foreskin fibroblast cell line by the XTT method. Our results showed that the water extract of P. lobata could inhibit cytopathy induced by EV71 when given before (p < 0.0001), simultaneously with (p < 0.0001), or after viral infection (p < 0.0001). Water extract of P. lobata was effective and its minimal concentration that inhibited 50% of the cytopathic effect (IC50) was 0.028 microg/mL. P. lobata was also safe with a selectivity index greater than 107,000. Water extract of P. lobata appeared to inhibit viral attachment (p < 0.0001) and penetration (p < 0.0001). The anti-EV71 activity of the water extract of P. lobata was not mediated by interferons. In conclusion, the water extract of P. lobata was effective in the management of the disease induced by EV71 infection.
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