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Updated: Apr 11, 2026
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
Shuya Yano1,2,3, Shinji Miwa1,2, Hiroyuki Kishimoto3
1AntiCancer, Inc., San Diego, CA, USA.
Abstract:
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.
Insights
High-dose fluorescence-guided surgery (FGS) using OBP-401 adenovirus effectively labels and eradicates soft-tissue sarcoma (STS) in mice. This novel FGS approach offers a potential cure for currently incurable STS by preventing recurrence and preserving muscle function.
Area of Science:
- Oncology
- Surgical Innovation
- Gene Therapy
Background:
- Fluorescence-guided surgery (FGS) shows promise for cancer treatment but struggles with residual microscopic disease.
- Current FGS methods lack curative potential due to incomplete tumor resection.
Purpose of the Study:
- To evaluate the efficacy of OBP-401-mediated FGS in an orthotopic soft-tissue sarcoma (STS) model.
- To determine if OBP-401-based FGS can achieve complete tumor eradication and prevent recurrence.
Main Methods:
- Human fibrosarcoma HT1080 cells expressing RFP were implanted in nude mice.
- Tumors were labeled with GFP using a telomerase-dependent adenovirus (OBP-401).
- OBP-401-based FGS and bright light surgery (BLS) were compared for tumor resection and outcomes.
Main Results:
- OBP-401 successfully labeled STS tumors with GFP.
- OBP-401-based FGS demonstrated superior resection compared to BLS.
- High-dose OBP-401 FGS resulted in no residual tumor cells, local recurrence, or metastasis, improving disease-free survival and preserving muscle function.
Conclusions:
- High-dose OBP-401-based FGS can potentially cure soft-tissue sarcoma, a currently incurable disease.
- The dual action of OBP-401 (labeling and killing cancer cells) is key to its efficacy.
- OBP-401-FGS technology is expected to be clinically translatable due to the established safety of its parent virus (OBP-301).
