Abstract |
The role of the bystander effect in the treatment of a human breast carcinoma xenograft was studied by suicide gene therapy with carboxypeptidase G2 (CPG2) and CMDA. Cells expressing enzymatically active surface-tethered bacterial CPG2 [stCPG2(Q)3] were mixed with control beta-galactosidase (beta-Gal)-expressing cells to give stCPG2(Q)3:beta-Gal ratios of, respectively: group 1, 0:100; group 2, 10:90; group 3, 50:50; and group 4, 100:0. Four days after injection of the cells into nude mice, the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl- L-glutamic acid ( CMDA) was administered. Tumor growth delay correlated well with the levels of stCPG2(Q)3 expression: group 1, 0 day delay; group 2, 10 days; group 3, 16 days; and group 4, 90 days. Similarly, the number of cures was strongly correlated to the levels of stCPG2(Q)3 activity: group 1, zero of six cured; group 2, one of six cured; group 3, three of six cured and group 4, four of six cured. There was a good correlation between CPG2 enzyme activity in the tumors and the number of cures. The majority of cells from groups 2 and 3 were apoptotic whereas those from group 1 were not, indicating a substantial bystander effect in the tumors. These results suggest that a bystander effect plays a major role in suicide gene therapy regimens with stCPG2(Q)3 and CMDA.
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Authors | S M Stribbling, F Friedlos, J Martin, L Davies, R A Spooner, R Marais, C J Springer |
Journal | Human gene therapy
(Hum Gene Ther)
Vol. 11
Issue 2
Pg. 285-92
(Jan 20 2000)
ISSN: 1043-0342 [Print] United States |
PMID | 10680842
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Glutamates
- Nitrogen Mustard Compounds
- Prodrugs
- 4-((2-chloroethyl)(2-mesyloxyethyl)amino)benzoylglutamic acid
- gamma-Glutamyl Hydrolase
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Body Weight
(drug effects)
- Breast Neoplasms
(drug therapy, genetics)
- Female
- Genetic Therapy
(methods)
- Glutamates
(pharmacology)
- Humans
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
- Nitrogen Mustard Compounds
(pharmacology)
- Prodrugs
(pharmacology)
- Time Factors
- gamma-Glutamyl Hydrolase
(genetics)
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