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The FASEB Journal, Vol 4, 188-193, Copyright © 1990 by The Federation of American Societies for Experimental Biology

REVIEWS

Activation of prodrugs by antibody-enzyme conjugates: a new approach to cancer therapy

PD Senter
Oncogen, Seattle, Washington 98121.

A new strategy for the delivery of cytotoxic agents to solid tumors is described in which monoclonal antibodies are used as carriers for enzymes to tumor cell surfaces. The enzymes are chosen for their abilities to convert relatively noncytotoxic drug precursors (pro- drugs) into active anticancer drugs. The drugs thus formed can then penetrate into nearby tumor cells, resulting in cell death. A number of prodrugs have been developed that can be transformed into active anti- cancer drugs by enzymes of both mammalian and non-mammalian origin. The enzymes have been shown to localize into tumors when linked to monoclonal antibodies that bind to tumor-associated antigens. In vivo studies indicate that MAb-enzyme/prodrug combinations can result in antitumor activities significantly greater than those of the prodrugs or drugs given alone. This is most likely due to the generation of large amounts of active drug at the tumor site.


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