Co-transduction of herpes simplex virus thymidine kinase gene and human interleukin-2 gene into mouse ovarian cancer cell line, OVHM

We studied the thymidine kinase (TK) gene and the interleukin (IL)-2 gene c o-transduction into tumor cells for a possible strategy of cancer gene ther apy. A murine ovarian cancer cell line, OVHM, was retrovirally transduced w ith the TK (OVHM/TK) or the IL-2 gene (OVHM/IL-2.). The TK or IL-2 expressi on was permanent in OVHM/TK or OVHM/IL-2. OVHM/TK cells were susceptible to gancyclovir (GCV) in vitro, and their intraperitoneal growth was completel y regulated with GCV administration. The bystander effect was not observed in vitro and in vivo in this model, and only the marginal emergence of immu ne involvement was observed in the OVHM/TK-cured mice with GCV. OVHM/IL-2 c ells produced IL-2 biologically active to be immunogenic, but still tumorig enic to kill the mice when inoculated intraperitoneally. Then, OVHM/TK cell s were co-transduced with the IL-2 gene to establish OVHM/TK/IL-2 cells. OV HM/TK/IL-2 cells were also susceptible to GCV and transiently produced acti ve IL-2. A significant resistance against the challenge of parental tumor c ells was observed in the mice that were inoculated with OVHM/TK/IL-2 cells and cured with GCV administration. It is suggested that tumor cells transdu ced with both TK and IL-2 genes could be regressed with GCV administration with subsequent generation of immune activation in the host. Since the byst ander effect may not always be a common phenomenon in gene therapy using th e TK gene, this type of combination may be advantageous in the clinical app lication of gene therapy for human cancers.