دورية
A Phase I/II Dose-Escalation Study of Herpes Simplex Virus Type 1 Thymidine Kinase Suicide Gene Therapy for Metastatic Melanoma
| العنوان: | A Phase I/II Dose-Escalation Study of Herpes Simplex Virus Type 1 Thymidine Kinase Suicide Gene Therapy for Metastatic Melanoma |
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| المؤلفون: | Klatzmann, David, Chrin, Patrick, Bensimon, Gilbert, Boyer, Olivier, Coutellier, Anne, Charlotte, Frdric, Boccaccio, Catherine, Salzmann, Jean-Loup, Herson, Serge |
| المصدر: | Human Gene Therapy; November 20, 1998, Vol. 9 Issue: 17 p2585-2594, 10p |
| مستخلص: | ABSTRACTWe performed a dose-escalating phase I/II study of retrovirus-mediated herpes simplex virus type 1 thymidine kinase (HSV-1-TK) suicide gene therapy for metastatic melanoma. HSV-1 TK expression, which specifically sensitizes transduced and bystander cancer cells to ganciclovir (GCV) toxicity, was mediated by one (four patients, first dose step) to three (four patients, second dose step) injections of M11 retrovirus vector-producing cells in melanoma cutaneous nodules. After a 7-day period allowed for cancer cell transduction, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by tumor measurements and histology. M11 doses ranged from 76 to 1247 106cells. Treatment-related adverse events were mild and transient, limited to inflammatory skin reactions at injection and fever on repeated injections. Plasma GCV was in the active range (>0.2 g/ml); transgene was detected by polymerase chain reaction in three of six patients; treated tumor size was moderately affected under GCV as compared with untreated tumors, although 2 weeks after GCV administration important (>50%) treated-tumor necrosis was evidenced on histology in three of eight patients. All patients showed disease progression on long-term follow-up. Thus, M11-mediated HSV-1 TK gene therapy was well tolerated over a wide dose range. The limited tumor response is likely to be related to poor gene transfer efficiency. However, necrosis following GCV administration in transduced tumors indicates a potential for treatment efficacy. |
| قاعدة البيانات: | Supplemental Index |
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