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 (T Kh) and ganciclovir (GCV) treatment has revealed an important intratum oral bystander effect, A whole tumor can be eliminated when only a fra ction 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 TK h(-) tumors in different rat liver lobes such that there was no contac t 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 imm une mediated, should be of major importance for gene therapy of dissem inated tumors.