A method for increasing the target-specific toxicity of a drug is effected
by pretargeting an enzyme to a mammalian target site, and then
administering a cytotoxic drug known to act at the target site, or a
prodrug form thereof which is converted to the drug in situ, which drug
is also detoxified to form an intermediate of lower toxicity using said
mammal's ordinary metabolic processes, whereby the detoxified
intermediate is reconverted to its more toxic form by the pretargeted
enzyme and thus has enhanced cytotoxicity at the target site. Further
enhancement can be achieved by pretargeting an enzyme which converts the
prodrug to the cytotoxic drug at the target site. Kits for use with the
method also are provided. The method and kits permit lower doses of
cytotoxic agents, maximize target site activity and minimize systemic
side effects.