Suicide Gene Therapy
Transfer of drug-activating enzyme gene into tumor cells and treatment with a prodrug form of chemotherapeutic agents causes a high concentration of the activated drug in the tumor tissue and apoptosis of tumor cells. Not only transduced cells, but also circumferential cells are reported to die with this gene therapy (bystander effect).
A clinical trial of retroviral herpes simplex virus thymidine kinase (HSV-TK) gene transfer into breast cancer tumor tissues and treatment with gancylovir is ongoing (Favrot).
A phase I study of injection of HER2 promoter-driven cytosine deaminase (CD) gene plasmid into metastatic skin lesions of breast cancer and treatment with prodrug (fluorocytosine) has been reported. Fluorocytosine is transformed into 5FU by the CD gene. Expression of the CD gene in HER2-positive tumor cells has been shown in 9/11 cases at day 2 and 3/10 cases at day 7. Tumor reduction was shown in 4 of 12 cases21).
Retroviral P450 2B6 (CYP2B6) gene transfer into metastatic cutaneous tissues and oral cyclophosphamide therapy causes efficient conversion of prodrug cyclophosphamide into active metabolite phosphoramide mustard in the tumor tissues.
In a phase I study, nine breast cancer and three melanoma patients were treated with CYP2B6 vector (MetXia-P450). One breast cancer patient had a PR and four (33%) had stable diseases (SD) ≥ 3 months22).