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Porcine Corneal Tissue Explant to Study the Efficacy of Herpes Simplex Virus-1 Antivirals
Published on: September 20, 2021
High therapeutic potential for systemic delivery of a liposome-conjugated herpes simplex virus
Toshio Shikano1, Hideki Kasuya, Tevfik Tolga Sahin
1Department of Surgery II, Nagoya University Graduate School of Medicine, Tsuruma-cho, Showa-ku, Japan.
Purpose:
Oncolytic viral therapy is a newly developed modality to treat tumors. Many clinical trials worldwide have examined the efficacy of locally injected oncolytic viruses. However, systemic intravascular injections are limited by the humoral immune response, which dramatically decreases the level of infection. To overcome this limitation, we encapsulated the oncolytic virus in liposomes.
Methods:
The infectious properties of the herpes simplex virus type 1 (HSV-1) mutant, hrR3, with or without liposomes in the presence of neutralizing antibodies were evaluated using replication and cytotoxicity assays in vitro. To evaluate the efficacy of intravascular virus therapy with liposomes in the presence of neutralizing antibodies, immunized mice bearing multiple liver metastases were intraportally or peritoneally administered hrR3 or hrR3 complexed with liposomes.
Results:
Anti-HSV antibodies attenuated the infectiousness and cytotoxicity of hrR3, whereas hrR3/liposome complexes were not attenuated by these anti-HSV antibodies. Although the survival rate of non-immunized mice treated with hrR3 alone was similar to that of mice treated with the hrR3/liposome complexes, the survival rates of immunized mice treated with hrR3 alone were significantly reduced compared to mice treated with the hrR3/liposome complexes.
Conclusions:
This systemic intravascular delivery of hrR3/liposome complexes in the presence of pre-existing neutralizing antibodies is effective to treat multiple liver metastases.
Insights
Liposome encapsulation protects oncolytic viruses from immune responses, enhancing their effectiveness for treating liver metastases via systemic delivery. This approach overcomes limitations of traditional viral therapies.
Area of Science:
- Oncolytic virotherapy
- Nanomedicine
- Immunology
Background:
- Oncolytic viral therapy offers a novel approach to cancer treatment.
- Systemic administration of oncolytic viruses is hindered by humoral immune responses.
- Liposome encapsulation is explored to shield viruses from immune detection.
Purpose of the Study:
- To evaluate the efficacy of liposome-encapsulated oncolytic virus (herpes simplex virus type 1 mutant hrR3) for systemic intravascular delivery.
- To determine if liposomes can protect hrR3 from neutralizing antibodies.
- To assess the therapeutic effect on liver metastases in an in vivo model.
Main Methods:
- In vitro assays assessed the infectivity and cytotoxicity of hrR3 with and without liposomes in the presence of neutralizing antibodies.
- Mice with liver metastases were administered hrR3 or liposome-complexed hrR3 via intraportal or peritoneal injection.
- Survival rates were compared between treatment groups, including immunized and non-immunized mice.
Main Results:
- Neutralizing antibodies significantly reduced the infectivity and cytotoxicity of free hrR3.
- Liposome-encapsulated hrR3 (hrR3/liposome complexes) remained unaffected by neutralizing antibodies.
- Immunized mice treated with hrR3/liposome complexes showed significantly improved survival compared to those treated with hrR3 alone.
Conclusions:
- Systemic intravascular delivery of liposome-complexed hrR3 is effective in treating multiple liver metastases.
- Liposome encapsulation successfully overcomes the limitations posed by pre-existing neutralizing antibodies.
- This strategy enhances the therapeutic potential of oncolytic viruses for disseminated cancers.
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