[hTERT promoter-based conditionally replicative adenoviruses are useful for lung cancer and other solid cancer treatment].
Treatment of advanced SCLC remains one of the major challenges in current medicine because of the high morbidity and mortality of the disease. Advanced stage lung cancer is refractory to conventional therapies and it also has an extremely poor prognosis. As a result, new therapeutic approaches are needed. Telomere maintenance to the regulation of replicative life span strongly implies that alterations in telomere biology play an important role during malignant transformation. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers were examined in a previous study. In this study, we turned the expression of hTERT by tumors to a therapeutic advantage using a conditionally replication-competent adenovirus (CRAd) in which the expression of E1 is controlled by the hTERT promoter. This virus achieved good levels of viral replication in SCLC cells and induced a substantial anti-cancer effect in vitro and in vivo. As a further enhancement the cancer cell killing effect was improved with a tropism modification of the virus to express the knob domain of Ad3, and this improved infectivity for cancer cells. Conversely, the hTERT promoter has low activity in normal tissues, and the CRAd caused no damage to normal lung fibroblast cells. Since the telomerase activity is common in many types of cancers, these CRAds may be applicable to a wide range of tumors. We concluded that the use of hTERT promoter-based CRAds may be a potentially effective strategy for cancer treatment.
Uchino
Junji
J
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582, Japan.
Takayama
Koichi
K
Harada
Akiko
A
Kawakami
Yosuke
Y
Inoue
Hiroyuki
H
Curiel
David T
DT
Nakanishi
Yoichi
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D011401:Promoter Regions, Genetic; D055752:Small Cell Lung Carcinoma / Q000628:therapy*; D019098:Telomerase / Q000032:analysis*; D014407:Tumor Cells, Cultured
D019098:Telomerase