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Published on: January 7, 2019
Immune safety of a novel oncolytic mutant M1 after administration in vivo
Lijun Jiang1, Xiaoxi Zhou1, Qinlu Li1
1Department of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China.
Abstract:
The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.
Insights
This study found that the novel oncolytic adenovirus mutant M1 is safe for in vivo use. Combining M1 with immunosuppressive agents improved its safety and effectiveness in animal models.
Area of Science:
- Oncolytic virotherapy
- Immunology
- Pharmacology
Background:
- Oncolytic viruses offer a promising cancer treatment strategy.
- Optimizing the delivery and safety of oncolytic viruses is crucial for clinical translation.
- Immunosuppressive agents may modulate the host response to oncolytic virus therapy.
Purpose of the Study:
- To assess the safety and efficacy of a novel oncolytic adenovirus mutant (M1).
- To evaluate the impact of combining M1 with immunosuppressive agents.
- To investigate the biodistribution and host immune response to M1 administration.
Main Methods:
- Administration of M1 via intravenous and retroperitoneal routes in animal models.
- Monitoring of liver and renal function (ALT, Scr).
- Histopathological examination of liver tissue and immunohistochemical analysis for viral expression.
- Analysis of lymphocyte recruitment and adenovirus-specific T cell activation.
Main Results:
- M1 administration showed transient increases in ALT and Scr, with mild liver inflammation.
- Retroperitoneal injection resulted in higher adenoviral protein expression compared to intravenous injection.
- Combined treatment with cyclosporine A ameliorated liver/kidney dysfunction and increased M1 concentration in the liver.
Conclusions:
- The novel oncolytic adenovirus mutant M1 demonstrates an acceptable safety profile in vivo.
- Co-administration of M1 with immunosuppressive agents enhances its therapeutic effectiveness and safety.
- This combination strategy holds potential for improving oncolytic virotherapy outcomes.
