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Modeling oncolytic virus dynamics in the tumor microenvironment using zebrafish
David Mealiea1,2,3, Emilie Boudreau4, Naomi De Silva4
1Department of Surgery, University of Toronto, Toronto, Ontario, Canada. d.mealiea@mail.utoronto.ca.
Abstract:
We have adapted a zebrafish (Danio rerio) tumor xenograft model for use in the study of oncolytic virotherapy. Following implantation of mammalian cancer cells into the perivitelline space of developing zebrafish embryos, both local and intravenous oncolytic virus treatments produce a tumor-specific infection with measurable antitumor effects. Tumor cells are injected at 48 h post fertilization, with oncolytic virus treatment then being administered 24 h later to allow for an initial period of tumor development and angiogenesis. Confocal fluorescent imaging is used to quantify dynamics within the tumor environment. The natural translucency of zebrafish at the embryo stage, coupled with the availability of strains with fluorescent immune and endothelial cell reporter lines, gives the model broad potential to allow for real time, in vivo investigation of important events within tumors throughout the course of virotherapy. Zebrafish xenografts offer a system with biologic fidelity to processes in human cancer development that influence oncolytic virus efficacy, and to our knowledge this is the first demonstration of the model's use in the context of virotherapy. Compared with other models, our protocol offers a powerful, inexpensive approach to evaluating novel oncolytic viruses and oncolytic virus-based combination therapies, with potential application to investigating the impacts of virotherapy on immune response, tumor vasculature, and metastatic disease.
Insights
Researchers developed a zebrafish tumor xenograft model for oncolytic virotherapy. This inexpensive, real-time model shows measurable antitumor effects and aids in studying virotherapy
Area of Science:
- Oncolytic Virotherapy
- Cancer Research
- Zebrafish Models
Background:
- Oncolytic virotherapy utilizes viruses to selectively target and destroy cancer cells.
- Developing effective and accessible preclinical models is crucial for advancing virotherapy research.
- Existing models may lack the biological fidelity or cost-effectiveness for comprehensive virotherapy studies.
Purpose of the Study:
- To adapt and validate a zebrafish (Danio rerio) tumor xenograft model for studying oncolytic virotherapy.
- To demonstrate the model's capability for real-time, in vivo investigation of virotherapy dynamics.
- To establish a cost-effective platform for evaluating novel oncolytic viruses and combination therapies.
Main Methods:
- Mammalian cancer cells were xenografted into zebrafish embryos (48 hours post-fertilization).
- Oncolytic virus treatment was administered 24 hours post-tumor cell injection.
- Confocal fluorescent imaging was employed to quantify tumor microenvironment dynamics.
Main Results:
- The zebrafish model demonstrated tumor-specific infection and measurable antitumor effects following oncolytic virus treatment.
- The model allows for real-time, in vivo visualization of tumor and immune cell interactions during virotherapy.
- The system exhibits biological fidelity to human cancer development processes relevant to virotherapy efficacy.
Conclusions:
- The adapted zebrafish xenograft model is a powerful and inexpensive tool for oncolytic virotherapy research.
- This model facilitates the evaluation of novel oncolytic viruses and combination therapies.
- It offers potential for investigating the impact of virotherapy on immune response, tumor vasculature, and metastasis.
