[Specific in vitro effects of methotrexate entrapped into liposomes bearing antibody fragments against human chorionic gonadotropin on cell growth of cultured human choriocarcinoma cells].
Methotrexate (MTX) was entrapped into liposomes, to which rabbit antibody fragments (Fab') against human chorionic gonadotropin (hCG) had been coupled covalently, using N-[4-(p-maleimidophenyl) butyryl] phosphatidyl ethanolamine. By this system, The resulting molar ratio in the prepared liposomes was 15 MTX per Fab', and the activities of both MTX and the antibody were well preserved. The inhibitory effects of MTX entrapped in liposomes bearing anti-hCG Fab' (Lip[MTX, anti-hCG]) on the growth of choriocarcinoma cells (BeWo) in vitro were examined. The 50% inhibitory concentration of Lip[MTX, anti-hCG] was found to be 1 X 10(-3) micrograms MTX/ml, which was significantly lower than the concentrations of control groups, free MTX (2.5 X 10(-3) micrograms/ml) or MTX entrapped in liposomes bearing no antibody (Lip [MTX], 1.3 X 10(-2) micrograms/ml). The effect of the coupling of the specific antibody was more clearly demonstrated by a short-time incubation (60 min) experiment. Lip [MTX, anti-hCG] exhibited marked inhibition on cell growth, compared to MTX entrapped in liposomes bearing non-immunized Fab' (Lip[MTX, non-immunized Fab']). On the other hand, free MTX showed no effect in this experiment. We may conclude that Lip [MTX, anti-hCG] has a specific inhibitory effect on the growth of choriocarcinoma cells in vitro, which suggests the possibility of a specific immunochemotherapy for this disease, using the specific antibody to this tumor coupled to liposomes.
D000906:Antibodies / Q000008:administration & dosage*; D002455:Cell Division; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000473:pathology*; D006063:Chorionic Gonadotropin / Q000276:immunology*; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000473:pathology*
D000906:Antibodies; D006063:Chorionic Gonadotropin; D008081:Liposomes; D008727:Methotrexate