A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor.
Antitumor gene therapy using herpes simplex type 1 thymidine kinase (TKh) and ganciclovir (GCV) treatment has revealed an important intratumoral bystander effect. A whole tumor can be eliminated when only a fraction of its tumor cells express TKh. We now report that the bystander effect not only acts within a tumor, but also between distant tumors. One TKh+ tumor was generated simultaneously with one or multiple TKh- tumors in different rat liver lobes such that there was no contact between the resulting tumors. Both the TKh+ and the TKh- tumors regressed after GCV treatment and showed infiltration with macrophages and T lymphocytes. This distant bystander effect, which is likely immune mediated, should be of major importance for gene therapy of disseminated tumors.
Kianmanesh
A R
AR
Laboratoire de Recherches Chirurgicales, Hôpital Cochin, Paris-V University, France.
Perrin
H
H
Panis
Y
Y
Fabre
M
M
Nagy
H J
HJ
Houssin
D
D
Klatzmann
D
D
D016475:3T3 Cells; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002472:Cell Transformation, Viral; D003110:Colonic Neoplasms / Q000556:secondary / Q000628:therapy*; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D051381:Rats; D012074:Remission Induction; D013937:Thymidine Kinase / Q000235:genetics* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir