Cytopathic effect of in situ gene therapy in prostate cancer.
This is a morphologic study of in situ gene therapy effects in patients with prostate cancer using the Herpes Simplex VirusThymidine Kinase gene (HSV-tk) followed by ganciclovir. Prostatectomy specimens from the first 4 patients showed the following morphologic changes: (1) various degrees of necrosis were seen in cancer foci; (2) cytopathic changes were seen across the whole spectrum of Gleason grades; (3) the normal prostate was rarely affected by necrosis, but contained an intense mononuclear infiltrate; (4) loss of nuclear detail was a common finding. Volumetric studies showed that only portions of the tumor show morphologic effects as well as an inverse relationship between percentage of affected tumor and prostate and tumor size. An inflammatory response was observed, with predominance of CD20-positive cells in normal prostate tissue, CD8 (cytotoxic T cells) in the tumor, and macrophages in all areas of the treated prostates. We believe that these changes represent the cytopathic effect of our in situ gene therapy on prostate cancer, and that they trigger a local immune response.
Department of Pathology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
G
G
Ayala
T M
TM
Wheeler
M
M
Shalev
T C
TC
Thompson
B
B
Miles
E
E
Aguilar-Cordova
S
S
Chakraborty
D
D
Kadmon
D000368:Aged; D018951:Antigens, CD20 / Q000032:analysis; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002467:Cell Nucleus / Q000473:pathology; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011467:Prostate / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D017154:Stromal Cells / Q000473:pathology; D013937:Thymidine Kinase / Q000235:genetics
D018951:Antigens, CD20; D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir