Kianmanesh A R, Perrin H, Panis Y, Fabre M, Nagy H J, Houssin D, Klatzmann D
Laboratoire de Recherches Chirurgicales, Hôpital Cochin, Paris-V University, France.
Hum Gene Ther. 1997 Oct 10;8(15):1807-14. doi: 10.1089/hum.1997.8.15-1807.
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.
使用单纯疱疹病毒1型胸苷激酶（TKh）和更昔洛韦（GCV）治疗的抗肿瘤基因疗法已显示出重要的肿瘤内旁观者效应。当仅一小部分肿瘤细胞表达TKh时，整个肿瘤就可以被消除。我们现在报告，旁观者效应不仅在肿瘤内起作用，而且在远处的肿瘤之间也起作用。在不同的大鼠肝叶中同时产生一个TKh +肿瘤和一个或多个TKh-肿瘤，使得产生的肿瘤之间没有接触。GCV治疗后，TKh +和TKh-肿瘤均消退，并显示有巨噬细胞和T淋巴细胞浸润。这种可能由免疫介导的远处旁观者效应对于播散性肿瘤的基因治疗应该具有重要意义。
