Efficacy and selectivity of vindesine monoclonal anti-carcinoembryonic antigen antibody conjugates on human tumor cell lines grown as xenografts in nude mice

The therapeutic potential of immunoconjugates comprising vindesine and a monoclonal anti-CEA antibody, 11-285-14, has been evaluated in vivo using a clinically relevant targeting model system. Treatment of nude mice bearing human tumor xenografts of varying target antigen (CEA) expression has demonstrated efficacy and selectivity of conjugates of vindesine with 11-285-14 on tumor growth for tumors expressing the antigen (LS174T and BENN) but not for those lacking the antigen (COLO320DM). An effect of conjugate was seen even with xenografts that achieved a no-growth state (SKCO1) but not with CEA-expressing xenografts that were resistant to free drug (SW1116). Additionally, prolonged survival of mice bearing a lung tumor xenograft was observed after conjugate treatment. The toxicity of conjugated drug was less than that of free drug, and conjugates retained efficacy up to 5 months after preparation.