Drug localisation and growth inhibition studies of vindesine-monoclonal anti-CEA conjugates in a human tumour xenograft.
The distribution of tritiated vindesine (3H-VDS) was studied in the tissues and tumours of athymic mice bearing a human colorectal tumour xenograft. Selective tumour localisation was obtained when 3H-VDS was injected as a conjugate with a monoclonal anti-CEA antibody (11.285.14) but not as a conjugate with a non-binding monoclonal IgGl (Ag8) or as free succinoyl-VDS. The amounts of VDS that localised in the tumour following injections of 3H-VDS-11.285.14 increased in proportion to the amount injected, over a wide dose range. Conjugates prepared using the Fab fragments of 11.285.14 showed no evidence of selective tumour uptake in comparison with normal tissues. Various dose levels of VDS-11.285.14 conjugate and free VDS were studied for effects on the growth of the tumour xenograft. A growth inhibition of 50% was obtained at 1.5 mg/kg with free VDS and at 2.5 mg/kg with conjugated VDS. The conjugate was, however, considerably less toxic.
G F
GF
Rowland
R G
RG
Simmonds
V A
VA
Gore
C H
CH
Marsden
W
W
Smith
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D014316:Tritium; D014751:Vindesine / Q000008:administration & dosage / Q000378:metabolism*
D002272:Carcinoembryonic Antigen; D000939:Epitopes; D014316:Tritium; D014751:Vindesine