DEPT (medicine)
Directed enzyme prodrug therapy (DEPT) uses enzymes artificially introduced into the body to convert
Antibody-directed enzyme prodrug therapy (ADEPT)
ADEPT
ADEPT has shown antitumor activity in animal tumor models of human
ADEPT history
The first pilot-scale clinical trial of ADEPT was carried out at Charing Cross Hospital, London, using an anti-CEA F(ab′)2 antibody conjugated to the bacterial enzyme carboxypeptidase G2 (CPG2).[5]
The antibody used in the first ADEPT clinical trial was of murine origin and the enzyme was bacterial. Host antibodies to both components of the AEC were present in the blood of all non-immunosuppressed patients by day 10 after AEC infusion.[6] Several patients received ciclosporin since it had been shown in rabbits that this could delay the appearance of host antibodies to soluble proteins.[7]
A subsequent, small-scale trial at the Royal Free Hospital, London, used the same agents as in the Charing Cross Hospital trial but the protocol was modified to provide additional pharmacokinetic data and most patients received only a single course of treatment.[8]
Gene-directed enzyme prodrug therapy (GDEPT)
GDEPT is a
Virus-directed enzyme prodrug therapy (VDEPT)
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VDEPT is the term given to the use of a virus to deliver the gene for GDEPT. VDEPT can potentially be used to enhance the therapeutic potential of
Lectin-directed Enzyme-Activated Prodrug Therapy (LEAPT)
LEAPT is a variant of DEPT in which the manipulation of carbohydrates on the surface of the enzyme is used to target the enzyme activity to the cell in question.[10] This allows exploitation of the sometimes highly specific sugar-lectin interactions found in organisms, including humans. Proof-of-principle examples have shown delivery to target organs of enzymes that specifically release cytotoxics to treat tumours.
Polymer-directed enzyme prodrug therapy (PDEPT)
PDEPT uses
Clostridia-directed enzyme prodrug therapy (CDEPT)
CDEPT is the use of
The CDEPT strategy
Perhaps the most challenging issue in cancer treatment is how to reduce the side effects of the injected anti-cancer agents, which are of a high cytotoxicity potential. A widely used solution is to use enzymes which are able to convert a relatively non-toxic prodrug precursor into the active drug form(s). Clostridial-directed enzyme prodrug therapy (CDEPT)[14] is one of the possible approaches.
Solid
In CDEPT, a prodrug-converting enzyme expressed by a clostridial expression plasmid converts a prodrug into an active drug form within the tumor. While the prodrug is the inactive form and can be administrated to the blood, the products of the prodrug cleavage are highly cytotoxic and show their effect only in the vicinity of tumor cells.
Difficulties in the engineering of clostridial strains have restricted the application of other enzyme prodrug systems. So far, two enzymes have been applied in CDEPT: cytosine deaminase and nitroreductase.[19]
References
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- ^ Bagshawe KD, Sharma SK, Springer CJ, Antoniw P (1995). "Antibody directed enzyme prodrug therapy (ADEPT): a pilot scale clinical trial". Tumor Targeting. 1: 17–29.
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- ^ KD Bagshawe and M Napier, Early clinical studies with ADEPT. In: RG Melton and RJ Knox Editors, Enzyme-Prodrug Strategies for Cancer Therapy Kluwer Academic, London (1999), 199–207.
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