In Vivo Gene Transfer with Retroviral Vector-Producer Cells for Treatment of Experimental Brain Tumors

TLDR

Direct in situ gene delivery into proliferating tumors offers a promising therapeutic strategy, exploiting retroviral vectors’ selective transfer to dividing cells while sparing nondividing neural tissue. Rats with cerebral glioma received intratumoral injections of fibroblasts producing a retroviral vector carrying the HSV‑thymidine kinase gene, and after five days of in‑situ transduction the tumors were treated with ganciclovir. The vector‑ganciclovir therapy caused complete regression of gliomas both macroscopically and microscopically, demonstrating selective targeting of dividing tumor cells while sparing nondividing neural tissue.

Abstract

Direct in situ introduction of exogenous genes into proliferating tumors could provide an effective therapeutic approach for treatment of localized tumors. Rats with a cerebral glioma were given an intratumoral stereotaxic injection of murine fibroblasts that were producing a retroviral vector in which the herpes simplex thymidine kinase (HS-tk) gene had been inserted. After 5 days during which the HS-tk retroviral vectors that were produced in situ transduced the neighboring proliferating glioma cells, the rats were treated with the anti-herpes drug ganciclovir. Gliomas in the ganciclovir- and vector-treated rats regressed completely both macroscopically and microscopically. This technique exploits what was previously considered to be a disadvantage of retroviral vectors--that is, their inability to transfer genes into nondividing cells. Instead, this feature of retroviruses is used to target gene delivery to dividing tumor cells and to spare nondividing neural tissue.