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| Multimodal cancer treatment mediated by a replicating oncolytic virus that delivers the oxazaphosphorine/rat cytochrome P4502B1 and ganciclovir/herpes simplex virus thymidine kinase gene therapies |
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| Author(s): Aghi M, Chou TC, Suling K, Breakefield XO, Chiocca EA |
| Source: CANCER RESEARCH Volume: 59 Issue: 16 Pages: 3861-3865 Published: AUG 15 1999 |
| Times Cited: 78 References: 21 |
| Abstract: Multimodal therapy is generally more effective than single-agent treatment for cancer. rRp450 is an engineered herpes simplex viral mutant that replicates in and kills tumor cells in a relatively selective fashion. It also expresses, in infected cells, the cyclophosphamide (CPA)-sensitive rat cytochrome P450 2B1 (CYP2B1) and the ganciclovir (GCV)-sensitive herpes simplex virus thymidine kinase (HSV-TK) transgenes. We show that cultured rat 9L and human U87 Delta EGFR glioma cells, infected and lysed by rRp450, also exhibit supra-additive sensitivity to both CPA and GCV, as determined by Chou-Talalay synergy analysis. DNA cross-linking, assayed by ethidium bromide fluorescence, was significantly inhibited in the presence of GCV, suggesting that interactions between the CPA/CYP2B1 and GCV/HSV-TK gene therapies occurred at the level of DNA repair. In vivo, regression of 9L s.c. tumor volumes in athymic mice was achieved only by the multimodal treatment allowed by rRp450 viral oncolysis combined with CPA/CYP2B1 and GCV/HSV-TK gene therapies, whereas all other treatment combinations produced only tumor growth retardation. |
| Document Type: Article |
| Language: English |
| Reprint Address: Chiocca, EA (reprint author), Massachusetts Gen Hosp E, Mol Neurooncol Labs, Neurosurg Serv CNY 6, Charlestown, MA 02129 USA |
Addresses:
1. Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Labs, Boston, MA 02114 USA
2. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA
3. Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Therapeut Program, New York, NY 10001 USA
4. Cornell Univ, Grad Sch Med Sci, New York, NY 10001 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: 228KJ |
| ISSN: 0008-5472 |
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