The development of radioimmuntherapies and immunotoxins ("magic bullets") holds great promise for improved treatments of cancer (Click here for access to our recent overview). Such therapies allow antibodies to target delivery of toxins or isotopes to cancer cells. This affords considerable improvements in toxicity and also the destruction of metastatic or residual cancer which is one of the major factors contributing to cancer related morbidity. A related area of research that has recently achieved prominence is the development of chemotherapy prodrugs. This involves treatment with inactive prodrugs which are specifically activated in the tumor mileau. One particularly exciting example of this approach is antibody-directed enzyme prodrug therapy (ADEPT). This technology involves two-steps - firstly an antibody:enzyme fusion protein is administered, the antibody moiety of which causes cancer cells to become preferentially coated with the fusion protein; secondly a chemotherapy prodrug is administered that has been designed to be susceptible to activation by the fusion protein. CC1065 is a highly cytotoxic alkylating agent that cannot be used in the clinic due to excessive systemic toxicity. Researchers at Panorama Research Inc. have now modified this molecule linking it to cephalosporin which is susceptible to beta-lactamase activation. The resultant prodrug is considerable less cytotoxic than CC1065. The next stage of this research is to determine the ability of antibody:beta-lactamase fusion proteins to activate the prodrug. This is expected to be the case as has been shown previously for similar molecules such as cephalosporin-doxorubicin. It is therefore hoped that cephalosporin-CC1065 will display an excellent therapeutic margin when used alongside antibody:beta-lactamase fusion proteins. 

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