Enhancement of CD70-specific CAR T treatment by IFN-γ released from oHSV-1-infected glioblastoma

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• Glioblastoma (GBM) has a poor prognosis despite advanced treatments.
• Oncolytic viruses (OVs) show promise by stimulating immune responses and improving the tumor microenvironment (TME).
• Interferon-gamma (IFN-γ) is crucial for tumor cell apoptosis and T cell recruitment.

Purpose of the Study:

• To investigate if oncolytic herpes simplex virus-1 (oHSV-1) enhances the antitumor efficacy of CD70-specific chimeric antigen receptor (CAR) T cells.
• To determine the role of T cell infiltration and IFN-γ release in this enhanced efficacy.

Main Methods:

• In vitro studies assessed oHSV-1's effect on IFN-γ secretion and CAR T cell activity against tumor cells.
• Combination therapy of CD70-specific CAR T cells and oHSV-1 was evaluated in vitro for tumor degradation.
• An orthotopic xenotransplanted GBM animal model was used to assess combined therapy's antitumor efficacy and impact on TME.

Main Results:

• oHSV-1 stimulated tumor cell IFN-γ secretion, increasing T cell activity.
• CD70-specific CAR T cells effectively recognized and killed tumor cells in vitro.
• Combination therapy promoted tumor degradation by enhancing pro-inflammatory factors and reducing anti-inflammatory factors in vitro.
• Combined therapy demonstrated potent antitumor efficacy in vivo, increasing T and NK cells while decreasing regulatory T cells and TGF-β1 in the GBM TME.

Conclusions:

• oHSV-1 enhances the therapeutic efficacy of CD70-specific CAR T cells through increased intratumoral T cell infiltration and IFN-γ release.
• This combination strategy supports the use of CAR T therapy in GBM treatment regimens.
• The findings highlight a promising approach for improving glioblastoma treatment outcomes.