Prodrug-activated gene therapy: involvement of an immunological component in the "bystander effect".
The integration and expression of the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene in localized tumors results in tumor regression after the administration of the specific nucleoside analogue ganciclovir (GCV). Although only 10% to 20% of the tumor cells take up the HSV1-TK gene, the neighboring cells also die, a phenomenon termed "bystander effect.". In the present study, coinjection of the MC26 mouse colon carcinoma cell line and the HSV1-TK expressing retroviral packaging cell line followed after 7 days by the intraperitoneal administration of GCV resulted in almost total tumor regression in the immunocompetent BALB/c mice but not in immunocompromised athymic BALB/c mice. This suggested a strong cell-mediated immune component to the bystander effect.
Gagandeep
S
S
Department of Surgery, Royal Liverpool University Hospital, England.
Brew
R
R
Green
B
B
Christmas
S E
SE
Klatzmann
D
D
Poston
G J
GJ
Kinsella
A R
AR
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D016516:CD4-CD8 Ratio; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D015536:Down-Regulation; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D011355:Prodrugs / Q000627:therapeutic use; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics; D018709:Statistics, Nonparametric; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured
D011355:Prodrugs; D013937:Thymidine Kinase; D015774:Ganciclovir