Targeted enzyme prodrug therapy

There have been also attempts to prepare targeted drugs based on anthracyclines employing the recognition of some specific sugars by receptors on the tumor cells. Thus, a /3-glucoside derivative of adriamycin (41) was used in an antibody-directed enzyme-prodrug therapy (O Scheme 16) [53],... 

Bagshawe, K. D., Sharma, S. K., Springer, C. J., and Antoniw, P. (1995) Antibody directed enzyme prodrug therapy a pilot-scale clinical trial. Tumour Targeting 1,17-30. 

An important application of aldolase antibodies is prodrug activation in chemotherapeutic strategies. Activation of a prodrug into an active drug at the tumor site enables selective destruction of those tumor cells. This type of site-specific targeting is known as antibody-directed enzyme prodrug therapy (ADEPT) [25]. The ADEPT complex serves two functions. The antibody portion of the complex enables delivery of the drug directly to the tu-... 

Fig. 6.13. Schematic representation of a selective delivery obtained by antibody-directed en-zyme-prodrug therapy (ADEPT). An exogenous enzyme is coupled to a monoclonal antibody (mAb) targeted for tumor cells. In a second step, a prodrug is administered, which, as a selective substrate of the exogenous enzyme, will be selectively activated at the tumor site.

Antibody-dependent enzyme-mediated prodrug therapy (ADEPT) is a two- or sometimes three-step approach in which an antibody-enzyme fusion protein or conjugate is infused and allowed to localize to the tumor target (reviewed in Refs. 

---