Adenoviral-mediated suicide gene therapy for ovarian cancer

作者：Alvarez RD^*; Gomez Navarro J; Wang MH; Barnes MN; Strong TV; Arani RB; Arafat W; Hughes JV; Siegal GP; Curiel DT

来源：Molecular Therapy, 2000, 2(5): 524-530.

DOI：10.1006/mthe.2000.0194

• gene therapy
• recombinant adenovirus
• suicide gene therapy
• ovarian cancer

The purpose of this phase I study was to determine the potential efficacy of adenoviral-mediated suicide gene therapy in women with recurrent ovarian cancer. Fourteen patients were treated intraperitoneally with herpes simplex virus-thymidine kinase (HSV-TK)-encoding adenovirus (AdHSV-TK) in dosages ranging between 1 x 10(9) and 1 x 10(11) pfu. Beginning 2 days later, ganciclovir (GCV) was administered intravenously at a dose of 5 mg/kg bid for 14 days. Transient vector-associated fever was experienced by 4 of 14 (29%) treated patients. Other possible vector-associated constitutional symptoms, abdominal pain, and gastrointestinal symptoms were experienced by 6 of 14 (43%) treated patients. No other dose-limiting vector-specific side effects were noted. Of the 13 patients evaluable for response, 5 (38%) had stable disease and 8 (62%) had evidence of progressive disease. Molecular analysis of evaluable ascites samples demonstrated the presence of transgene DNA and RNA in most patients 2 days following Ad HSV-TK administration. Ten of 11 evaluable patients had an increase in anti-adenovirus antibody titer. These results suggest that treatment with AdHSV-TK in combination with GCV is feasible in the context of human ovarian cancer and tolerated at the dosages studied.

• 出版日期2000-11