Regulatable Transgene Expression for Preventionof Chemotherapy-Induced Peripheral Neuropathy
著者
川田, 大輔
(Kawata, Daisuke)
上位タイトル
Molecular therapy. Methods and clinical development
Vol.6,
No.15
(2017.
6)
,p.91-
101
識別番号
DOI
10.1016/j.omtm.2017.06.004
その他
PMID：28702476
博士論文情報
学位授与番号
10107A536
学位授与年月日
2019-9-30
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.
