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Hum Gene Ther. 1997 Oct 10;8(15):1807-14.

A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor.

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  • 1Laboratoire de Recherches Chirurgicales, Hôpital Cochin, Paris-V University, France.


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.

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