Cytopathic effect of in situ gene therapy in prostate cancer

This is a morphologic study of in situ gene therapy effects in patients wit h prostate cancer using the Herpes Simplex Virus-Thymidine Kinase gene (HSV -tk) followed by ganciclovir. Prostatectomy specimens from the first 4 pati ents showed the following morphologic changes: (1) various degrees of necro sis were seen in cancer foci; (2) cytopathic changes were seen across the w hole spectrum of Gleason grades; (3) the normal prostate was rarely affecte d by necrosis, but contained an intense mononuclear infiltrate; (4) loss of nuclear detail was a common finding. Volumetric studies showed that only p ortions of the tumor show morphologic effects as well as an inverse relatio nship between percentage of affected tumor and prostate and tumor size. An inflammatory response was observed, with predominance of CD20-positive cell s in normal prostate tissue, CD8 (cytotoxic T cells) in the tumor, and macr ophages in all areas of the treated prostates. We believe that these change s represent the cytopathic effect of our in situ gene therapy on prostate c ancer, and that they trigger a local immune response. Copyright (C) 2000 by W.B. Saunders Company.