Activation of prodrugs by antibody-enzyme conjugates: a new approach to cancer therapy.
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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Oncogen, Seattle, Washington 98121.
D000469:Alkaline Phosphatase; D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D043525:Cytosine Deaminase; D004798:Enzymes; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009700:Nucleoside Deaminases; D010399:Penicillin Amidase; D011355:Prodrugs / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D011623:gamma-Glutamyl Hydrolase
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004798:Enzymes; D011355:Prodrugs; D000469:Alkaline Phosphatase; D011623:gamma-Glutamyl Hydrolase; D010399:Penicillin Amidase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase