Yano Shuya, Miwa Shinji, Kishimoto Hiroyuki, Uehara Fuminari, Tazawa Hiroshi, Toneri Makoto, Hiroshima Yukihiko, Yamamoto Mako, Urata Yasuo, Kagawa Shunsuke, Bouvet Michael, Fujiwara Toshiyoshi, Hoffman Robert M
AntiCancer, Inc., San Diego, CA, USA.
Department of Surgery, University of California San Diego, CA, USA.
Oncotarget. 2015 May 30;6(15):13133-48. doi: 10.18632/oncotarget.3811.
Fluorescence-guided surgery (FGS) of cancer is an area of intense interest. However, FGS of cancer has not yet been shown to be curative due to residual microscopic disease. Human fibrosarcoma HT1080 expressing red fluorescent protein (RFP) was implanted orthotopically in the quadriceps femoris muscle of nude mice. The tumor-bearing mice were injected with high and low-dose telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401, which labeled the tumor with GFP. Fluorescence-guided surgery (FGS) or bright light surgery (BLS) was then performed. OBP-401 could label soft-tissue sarcoma (STS) with GFP in situ, concordant with RFP. OBP-401-based FGS resulted in superior resection of STS in the orthotopic model of soft-tissue sarcoma, compared to BLS. High-dose administration of OBP-401 enabled FGS without residual sarcoma cells or local or metastatic recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. High-dose OBP-401 based-FGS improved disease free survival (p = 0.00049) as well as preserved muscle function compared with BLS. High-dose OBP-401-based FGS could cure STS, a presently incurable disease. Since the parent virus of OBP-401, OBP-301, has been previously proven safe in a Phase I clinical trial, it is expected the OBP-401-FGS technology described in the present report should be translatable to the clinic in the near future.
癌症的荧光引导手术（FGS）是一个备受关注的领域。然而，由于存在残留的微小病灶，癌症的FGS尚未被证明具有治愈性。将表达红色荧光蛋白（RFP）的人纤维肉瘤HT1080原位植入裸鼠的股四头肌中。给荷瘤小鼠注射高剂量和低剂量的端粒酶依赖性、含绿色荧光蛋白（GFP）的腺病毒OBP-401，该病毒用GFP标记肿瘤。然后进行荧光引导手术（FGS）或强光手术（BLS）。OBP-401可在原位用GFP标记软组织肉瘤（STS），与RFP一致。与BLS相比，基于OBP-401的FGS在软组织肉瘤原位模型中能更好地切除STS。高剂量给予OBP-401可实现FGS，且无残留肉瘤细胞或局部或远处复发，这归因于其用GFP标记癌细胞和杀伤癌细胞的双重作用。与BLS相比，基于高剂量OBP-401的FGS改善了无病生存期（p = 0.00049）并保留了肌肉功能。基于高剂量OBP-401的FGS可以治愈目前无法治愈的STS。由于OBP-401的亲本病毒OBP-301先前已在I期临床试验中被证明是安全的，预计本报告中描述的OBP-401-FGS技术在不久的将来应可转化应用于临床。
