Suppression of Growth of a Human Colorectal Tumour in Nude Mice by Vindesine-Monoclonal ANTI-CEA Conjugates

Localization of an anti-CEA monoclonal antibody in colo-rectal carcinoma xenografts

“…The pattern of 11.285.14 antibody deposition in colon carcinoma xenografts is similar to that reported with other anti-CEA antibodies [2,13] and overall the indication is that tumour localized anti-CEA antibody-drug conjugates would be complexed at least partly with CEA secreted into turnout spaces rather than totally with antigen intimately associated with cell surfaces. Nevertheless previous therapeutic studies with the 11.285.14 antibody conjugated to vindesine have shown significant retardation of growth of a CEA producing colon carcinoma xenograft [19], the implication being that this therapeutic response was due to drug being targeted to tumour by the antibody. This argument is supported by the present demonstration of significant localization of the 11.285.14 antibody in CEA producing xenografts.…”

Drug localisation and growth inhibition studies of vindesine-monoclonal anti-CEA conjugates in a human tumour xenograft

“…It has been shown previously that repeated injections at 5 mg/kg produce marked inhibition of tumour growth [15,16]. In other therapeutic experiments, different dose levels have been used and compared with doses of free VDS.…”

“…The demonstration that such antibodies, when labelled with radioactive isotopes, can localise selectively in tumours of experimental animals [2,8,11] and in cancer patients [1,6] suggests that selective drug delivery could be obtained using monoclonal antibody-drug conjugates. In previous studies [15,16] it has been shown that conjugates of the anti-cancer alkaloid vindesine (VDS) with a range of anti-tumour monoclonal antibodies produced selective tumour cytotoxic and cytostatic effects in vitro and in vivo. Although it was shown that the antibody component of these conjugates would localise in tumour xenografts [16], no direct evidence has so far been provided to show selective targeting of the drug component.…”

Antitumor properties of vindesine-monoclonal antibody conjugates

“…Growth of the MAWI tumor was assessed at intervals by a volume measurement according to the formula 0.5 (dld2d3), where dl, d2, and d 3 represent the maximum length, width, and height of the tumor in millimeter, respectively. This formula was shown to provide a good correlation (coefficient of 0.98, n = 31) with the weight of excised tumors over a wide range of tumor weights [16].…”