Reversing Feedback Immunosuppression during Oncolytic Virotherapy of Pediatric High Grade Glioma
Pediatrics high grade gliomas (pHGGs) are the most frequent pediatric brain tumor with poor prognosis. Currently, standard-of-care (SOC) treatments cannot completely eradicate the tumor and do not significantly increase the patient survival rate. Accordingly, there is an unmet need to develop new therapeutic strategies against pHGGs. Recently, oncolytic virus (OV) treatment has provided a new immunotherapy direction for cancer therapy, which acts by both direct lysis of tumor cells and by activating the host anti-tumor immune response. We previously developed an OV that could increase anti-tumor efficacy and anti-tumor immune response. However, it also induces feedback immunosuppression, including IDO signaling pathway activation. Indoximod, a drug targeting IDO signaling, has been investigated in a phase I clinical trial in pediatric glioma patients by our co-Investigators. We propose to use Indoximod to block feedback immunosuppression to boost the immunotherapy efficacy of our newly developed OV.
The project goal is to develop effective immunotherapy strategies to improve the survival and prognosis of pediatric high grade glioma patients. Combination Indoximod, a phrase I clinical trial drug, with this OV agent has immediate translational significance and is expected to be significantly beneficial to pHGGs treatment in the future.