ADEPT therapy

Structure 139 represents a cephalosporin conjugate of SIN-1 13 that has been synthesized and evaluated as a /3-lactamase-dependent, nitric oxide-releasing conjugate with potential application in antibody-directed enzyme prodrug therapy (ADEPT) <2003BML1687>. 

Figure 13.7 Outline of antibody-directed enzyme prodrug therapy (ADEPT). Subsequent to its enzymatic activation, the active drug is taken up by the cell, upon which it exhibits a cytocidal effect. Refer to text for specific detail...

A review describes how penicillins and cephalosporins having S-aminosulfenamine side-chains at the 6- and 7-positions, respectively, may act as P-lactamase-dependent prodrugs either as antibiotics or in antibody-directed enzyme prodmg therapy (ADEPT) in the treatment of cancer <00T5699>. 

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.

The examples given above may not be the ones ultimately cleared for cancer therapy. They were selected here simply to illustrate the principles of the ADEPT and GDEPT strategies relevant to our context. 

I. Niculescu-Duvaz, F. Friedlos, D. Niculescu-Duvaz, L. Davies, C. J. Springer, Prodrugs for Antibody- and Gene-Directed Enzyme Prodrug Therapies (ADEPT and GDEPT) , Anti-Cancer Desing 1999,14, 517-538. 

K. D. Bagshawe, Antibody Directed Enzymes Revive Anti-Cancer Prodrugs Concept , Br. J. Cancer 1987, 56, 531-532 K. D. Bagshawe, Antibody-Directed Enzyme/Pro-drug Therapy (ADEPT) , Biochem. Soc. Trans. 1990, 18, 750-752. 

Y. L. Leu, S. R. Roffler, J. W. Chern, Design and Synthesis of Water-Soluble Glucuro-nide Derivatives of Campothecin for Cancer Prodrug Monotherapy and Antibody-Directed Enzyme Prodrug Therapy (ADEPT) , J. Med. Chem. 1999, 42, 3623 - 3628. 

Antibody-directed Enzyme Pro-drug Therapy (ADEPT)... 

Table 8.4. ADEPT strategies developed for cancer therapy.

Antibody-directed enzyme prodrug therapy (ADEPT) illustrates a further application of... 

ADEPT antibody directed enzyme prodrug therapy... 

Abbreviations. NMRI, nuclear magnetic resonance imaging Antp, antennapedia RES, reticuloendothelial system ADEPT, antibody-directed enzyme prodrug therapy TAT. 

Francis RJ, Sharma SK, Springer C, Green AJ, et al. 2002. A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours. Br J Cancer. 87 600-607. 

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