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Production of Genetically Engineered Golden Syrian Hamsters by Pronuclear Injection of the CRISPR/Cas9 Complex
Published on: January 9, 2018
Syrian hamster as a permissive immunocompetent animal model for the study of oncolytic adenovirus vectors
Maria A Thomas1, Jacqueline F Spencer, Marie C La Regina
1Molecular Microbiology and Immunology, Saint Louis University School of Medicine and Division of Comparative Medicine, Washington University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
Abstract:
Oncolytic adenoviruses represent an innovative approach to cancer therapy. These vectors are typically evaluated in immunodeficient mice with human xenograft tumors. However, in addition to being immunodeficient, this model is limited because normal and cancerous mouse tissues are poorly permissive for human adenovirus replication. This prompted us to search for a model that more accurately reflects the use of oncolytic adenoviruses in cancer patients. To this end, we developed a novel Syrian hamster model that is both immunocompetent and replication-permissive. We found that human adenovirus replicates well in Syrian hamster cell lines and confirmed replication in the lungs. Oncolytic adenovirus injection showed efficacy in three different hamster tumor models. Furthermore, i.t. oncolytic adenovirus injection resulted in suppression of primary and metastatic lesions, i.t. replication and necrosis, vector entrance into the bloodstream, replication in the liver and lungs, and anti-adenovirus antibody induction. Our findings show that the Syrian hamster is a promising immunocompetent model that is permissive to human adenovirus replication in tumors as well as normal tissues. Therefore, the Syrian hamster model may become a valuable tool for the field of oncolytic adenovirus vectors in which vector safety and efficacy can be evaluated.
Insights
A novel Syrian hamster model allows for better evaluation of oncolytic adenoviruses in cancer therapy. This immunocompetent model supports virus replication, demonstrating efficacy against tumors and aiding safety assessments.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Preclinical models
Background:
- Oncolytic adenoviruses offer innovative cancer treatment strategies.
- Current preclinical models using immunodeficient mice with xenografts have limitations in adenovirus replication.
- A more accurate model is needed to assess oncolytic adenovirus safety and efficacy in cancer patients.
Purpose of the Study:
- To develop and validate a novel Syrian hamster model for oncolytic adenovirus research.
- To assess the permissiveness of Syrian hamster tissues to human adenovirus replication.
- To evaluate the efficacy and safety of oncolytic adenoviruses in immunocompetent hamsters.
Main Methods:
- Development of a novel Syrian hamster model.
- Assessment of human adenovirus replication in Syrian hamster cell lines and tissues.
- Evaluation of oncolytic adenovirus efficacy in three different hamster tumor models.
- Analysis of vector biodistribution, tumor response, and immune response.
Main Results:
- Human adenovirus demonstrated robust replication in Syrian hamster cell lines and lung tissue.
- Oncolytic adenovirus injection showed significant efficacy in suppressing primary and metastatic tumors.
- Intratumoral injection led to virus replication, necrosis, systemic spread, and anti-adenovirus antibody induction.
- The Syrian hamster model proved permissive to adenovirus replication in both tumor and normal tissues.
Conclusions:
- The Syrian hamster is a promising immunocompetent and replication-permissive model for oncolytic adenoviruses.
- This model accurately reflects human adenovirus replication, crucial for evaluating vector safety and efficacy.
- The Syrian hamster model can advance the development of oncolytic adenovirus therapies for cancer patients.

