Asset Details
Do you wish to reserve the book?
Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material
Do you wish to request the book?
Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material
2001
Overview
An antibody-directed enzyme prodrug therapy (ADEPT) system against CEA-positive tumours is currently in phase I clinical trials. It consists of a prodrug, 4-[N,N-bis(2-iodoethyl) amino] phenoxycarbonyl
L
-glutamic acid (ZD2767P) and a conjugate of the F(ab’)
2
anti-CEA antibody A5B7 and the bacterial enzyme carboxypeptidase G2 (CPG2). ZD2767P is converted by antibody-targeted CPG2 into an active bifunctional alkylating drug (ZD2767) at the tumour site. The IC
50
value of the prodrug against the human colorectal tumour LS174T cell line was 55 ± 9 μM following a 1 h exposure. In contrast, co-incubation of ZD2767P with CPG2 resulted in 229-fold increase in activity. Using a modified comet assay, DNA interstrand cross links (ISC) were detected within 1 h of ZD2767P + CPG2 treatment and were repaired by 24 h. A clear dose–response was seen between the level of ISC, growth inhibition and ZD2767 concentration. Administration of a therapeutic dose of ZD2767P 72 h after the F(ab′)
2
A5B7 conjugate to mice bearing LS147T xenografts resulted in extensive ISC in the tumour after 1 h; repair was seen at 24 h. Tumour biopsies and peripheral lymphocytes were studied in 5 patients on the ADEPT phase I clinical trial. In 4 patients no ISC were detected. These patients also demonstrated poor localization of conjugate and no tumour response was seen. However a significant level of ISC was detected in one tumour biopsy, which also showed evidence of conjugate localization and clinical response. These studies demonstrate the application of the comet assay in the measurement of ISC in vitro and in clinical material and confirm that activation of ZD2767P results in the formation of DNA crosslinks. © 2001 Cancer Research Campaign
http://www.bjcancer.com
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antibodies - therapeutic use
/ Antineoplastic Agents, Alkylating - immunology
/ Antineoplastic Agents, Alkylating - therapeutic use
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Carcinoembryonic Antigen - immunology
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - pathology
/ Enzymes
/ Female
/ gamma-Glutamyl Hydrolase - metabolism
/ Humans
/ Immunoglobulin Fab Fragments
/ Mice
/ Nitrogen
/ Nitrogen Mustard Compounds - immunology
/ Nitrogen Mustard Compounds - therapeutic use
/ Oncology
/ Pharmacology. Drug treatments
/ Prodrugs
/ Regular
/ Transplantation, Heterologous
/ Tumors
