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Review

Antibody-directed enzyme prodrug therapy (ADEPT) for cancer

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Pages 1777-1789 | Published online: 23 Feb 2005

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  • ••First brief clinical report of ADEPT.
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  • •Mechanism of cell death by the ADEPT system.
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  • ABOAGYE EO, ARTEMOV D,SENTER PD, BHUJWALLA ZM: Intratumoral conversion of 5-fluorocytosine to 5-fluorouracil by monoclonal antibody-cytosine deaminase conjugates: noninvasive detection of prodrug activation by magnetic resonance spectroscopy and spectroscopic imaging. Cancer Res. (1998) 58:4075–4078.
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  • •Preclinical study of a novel prodrug.
  • SENTER PD, BEAM KS, MIXAN B, WAHL AF: Identification and activities of human carboxylesterases for the activation of CPT-11, a clinically approved anticancer drug. Bioconjug. Chem. (2001) 12:1074–1080.
  • •Use of human enzymes in ADEPT.
  • BIGNAMI GS, SENTER PD, GROTHAUS PG, FISCHER KJ, HUMPHREYS T, WALLACE PM: N-(4'-hydroxyphenylacetyl)palytoxin: a palytwdn prodrug that can be activated by a monoclonal antibody-penicillin G amidase conjugate. Cancer Res. (1992) 52:5759–5764.
  • BLAKEY DC, DAVIES DH, DOWELL RI et al.: Antitumor effects of an antibody-carboxypeptidase G2 conjugate in combination with phenol mustard prodrugs. Br. Cancer (1995) 72:1083–1088.
  • SHABAT D, LODE HN, PERTL U et al..: In vivo activity in a catalytic antibody-prodrug system: antibody catalyzedetoposide prodrug activation for selective chemotherapy. Proc. Nati Acad. Sci. USA (2001) 98:7528–7533.
  • •Use of catalytic antibody in ADEPT.
  • FRANCIS RJ, SHARMA SK, SPRINGER CJ et al.: A Phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours. Br. Cancer. (2002) 87:600–607.
  • ••ADEPT clinical trial usingantibody-enzyme conjugates without the clearing antibody and the new prodrug ZD2767P.
  • MAYER A, FRANCIS R, SHARMA SK et al.: A Phase I/II trial of antibody directed enzyme prodrug therapy (ADEPT) with MFECP1 and ZD2767P. Br. Cancer (2004) 91\(Suppl. 1):58.
  • ••First report of an ADEPT clinical trialusing a recombinant glycosylated fusion protein and the ZD2767P prodrug.
  • PEDLEY RB, SHARMA SK, BOXER GM et al.: Enhancement of antibody-directed enzyme prodrug therapy in colorectal xenografts by an antivascular agent. Cancer Res. (1999) 59:3998–4003.
  • •First report of ADEPT combination therapy.

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