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.