Cancer antibody-directed therapy

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>. 

W. A. Denny, W. R. Wilson, The Design of Selectively-Activated Anti-Cancer Prodrugs for Use in Antibody-Directed and Gene-Directed Enzyme Prodrug Therapies , J. Pharm. Pharmacol. 1998, 50, 387 - 394. 

M. P. Napier, S. K. Sharma, C. J. Springer, K. D. Bagshawe, A. J. Green, J. Martin, S. M. Stribbling, N. Cushen, D. O Malley, R. H. Begent, Antibody-Directed Enzyme Prodrug Therapy Efficacy and Mechanism of Action in Colorectal Carcinoma , Clin. Cancer Res. 2000, 6, 765-772. 

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. 

Whereas initially the focus on antibody-based therapies was on cancer, anti-TNFa antibodies in particular have recently proven powerful in the therapy of chronic inflammatory diseases such as inflammatory bowel disease and rhemnatoid arthritis [71], These antibodies complex serum TNFa, the clinical benefit to RA patients most likely being the reduction of pro-inflammatory IL-6 and acute phase protein levels [9], Although they are directed against soluble proteins and as such will not serve as a drug carrier, they do show that targeted, i.e. selective, interference with a specific molecule or process can have a powerful effect without significant concomitant toxicity. 

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. 

Schmidt, R Ungureanu, I. Duval, R. Pompon, A. Monneret, C. Cancer therapy a paclitaxel prodrug for ADEPT (antibody-directed enzyme prodrug therapy). Eur. J. Org. Chem., 2001, 2129-2134. 

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