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Experimental Curative Fluorescence-guided Surgery of Highly Invasive Glioblastoma Multiforme Selectively Labeled With
Shuya Yano1, Shinji Miwa2, Hiroyuki Kishimoto3
1AntiCancer, Inc., San Diego, California, USA; Department of Surgery, University of California San Diego, San Diego, California, USA; Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Abstract:
Fluorescence-guided surgery (FGS) of cancer is an area of intense current interest. However, although benefits have been demonstrated with FGS, curative strategies need to be developed. Glioblastoma multiforme (GBM) is one of the most invasive of cancers and is not totally resectable using standard bright-light surgery (BLS) or current FGS strategies. We report here a curative strategy for FGS of GBM. In this study, telomerase-dependent adenovirus OBP-401 infection brightly and selectively labeled GBM with green fluorescent protein (GFP) for FGS in orthotopic nude mouse models. OBP-401-based FGS enabled curative resection of GBM without recurrence for at least 150 days, compared to less than 30 days with BLS.
Insights
A novel fluorescence-guided surgery (FGS) strategy using OBP-401 effectively targets glioblastoma multiforme (GBM). This innovative approach achieved curative resection in mouse models, preventing recurrence for over 150 days, unlike standard surgery.
Area of Science:
- Oncolytic virotherapy
- Neurosurgery
- Cancer imaging
Background:
- Fluorescence-guided surgery (FGS) shows promise for cancer treatment but lacks curative strategies.
- Glioblastoma multiforme (GBM) is highly invasive and difficult to resect completely with current surgical methods.
- There is a critical need for advanced techniques to improve GBM resection and patient outcomes.
Purpose of the Study:
- To develop and evaluate a curative strategy for glioblastoma multiforme (GBM) using fluorescence-guided surgery (FGS).
- To investigate the efficacy of telomerase-dependent adenovirus OBP-401 for selective GBM labeling and resection.
Main Methods:
- Utilized telomerase-dependent adenovirus OBP-401 to infect and label GBM cells with green fluorescent protein (GFP).
- Performed fluorescence-guided surgery (FGS) on orthotopic nude mouse models with GBM.
- Compared surgical outcomes of OBP-401-based FGS with standard bright-light surgery (BLS).
Main Results:
- OBP-401 brightly and selectively labeled GBM, enabling precise visualization during surgery.
- OBP-401-based FGS resulted in curative resection of GBM in mouse models.
- Tumor recurrence was prevented for at least 150 days post-OBP-401 FGS, significantly longer than the <30 days observed with BLS.
Conclusions:
- Telomerase-dependent adenovirus OBP-401 provides a viable and effective strategy for curative fluorescence-guided surgery of glioblastoma multiforme.
- This novel FGS approach significantly improves resection completeness and extends survival in preclinical GBM models.
- OBP-401-based FGS represents a promising advancement for treating highly invasive brain tumors like GBM.
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