This project seeks to develop a new immunotherapy for children with relapsed neuroblastoma and medulloblastoma. These cancers of young children arise in the peripheral and central (brain) nervous systems, respectively, and have many common features that make them so aggressive and difficult to cure. Both are currently treated with very intensive chemotherapy and radiation therapy that are far too often ineffective, and even when cure is achieved, patients suffer lifelong disabilities directly related to their therapy. New therapeutic approaches are desperately needed.

Childhood solid tumors are aggressive cancers in children and adolescents that often reoccur or progress after remission (relapsed) or do not even respond to current treatments (refractory). Over the past 40 years, despite multiple therapeutic approaches, children and adolescents with these relapsed/refractory cancers have a dismal outcome (less than 5% of them will survive 1 year) in large part due to the resistance to therapies induced by the suppressive environment in the tumor. New therapeutic approaches are urgently needed to improve the survival of these patients.

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.

Retinoblastoma (RB) is the most common eye cancer, affecting ~8000 children every year worldwide. This cancer can form in one or both eyes of babies and toddlers. Untreated, RB can lead to death of the child, however even with treatment the tumor may respond poorly and requiring the eye to be removed in 50% of advanced cases. There is a need to better understand the mechanisms behind treatment resistance and relapse for children with RB. For a long time we were limited in understanding this because RB tumors cannot be directly biopsied due to risk of cancer spread outside the eye.

Radiation is the primary treatment for diffuse midline gliomas (DMGs). Unfortunately, the vast majority of these tumors recur within the radiation treatment field owing to the inherent resistance of these tumors to radiotherapy. Given that radiation kills tumor cells by inducing DNA double strand breaks (DSBs), experimental therapeutics which target the DNA damage response are promising strategies for improving radiation therapy outcomes.