Harnessing oncolytic virus-mediated antitumor immunity in an infected cell vaccine

Area of Science:

• Oncology
• Immunology
• Virology

Background:

• Oncolytic viruses (OVs) like VSV-Δ51 show promise in cancer treatment by stimulating T-cell responses.
• However, many tumors are resistant to direct OV treatment, limiting their therapeutic scope.

Purpose of the Study:

• To develop a novel oncolytic vaccine platform (infected cell vaccine, ICV) to broaden the applicability of OVs.
• To evaluate the efficacy of ICV, particularly with granulocyte-monocyte colony stimulating factor (GM-CSF) expression (VSVgm-ICV), in controlling tumor growth.

Main Methods:

• Developed an infected cell vaccine (ICV) platform using VSV-Δ51-infected tumor cells.
• Administered prophylactic immunization with ICV and VSVgm-ICV in mouse models.
• Assessed immune cell populations (dendritic cells, NK cells, T cells) and cytokine production (IFNγ) post-immunization and tumor challenge.

Main Results:

• Prophylactic immunization with ICV conferred protection against subsequent tumor challenge.
• VSVgm-ICV significantly enhanced therapeutic efficacy compared to ICV alone.
• Immunization with VSVgm-ICV induced maturation of dendritic and NK cells, leading to rapid infiltration of IFNγ-producing T and NK cells into tumors.
• The approach demonstrated efficacy in controlling established tumors.

Conclusions:

• The oncolytic vaccine platform using infected tumor cells is a potent strategy to stimulate antitumor immunity.
• VSVgm-ICV enhances immune responses and controls tumor growth, even in resistant models.
• This adaptable strategy holds broad potential for personalized cancer therapy due to VSV's tropism and tumor-specific antigens.