T Cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive leukemia with increased incidence in children, adolescents and young adults. Currently, the standard treatment of T-ALL patients is intensive chemotherapy with almost 70%, 5-year event free survival for pediatric patients. Moreover, such non-targeted therapies fail to address high-risk T-ALL subtypes, with less than 40% of the patients becoming long-term survivors in the case of one such subtype, the ETP T-ALL (a more immature, stem cell-like flavor of the disease).

Medulloblastoma is the most common malignant pediatric brain tumor. Current standard of the care of medulloblastoma is a combination of chemotherapy and radiation therapy. While this aggressive treatment regiment can potentially cure the disease, treatment-induced morbidities are devastating and furthermore, one third of patients relapse despite the treatment. Currently, there are no alternative therapies available for patients with recurrent tumors.

Our aim is to develop potent immune-based therapies for high-risk neuroblastoma that produce complete tumor responses without toxicity and without compromising quality of life.

We have already demonstrated that T-cells genetically modified to recognize the GD2 protein expressed on neuroblastoma cells can safely eliminate local relapsed neuroblastoma, but complete responses of bulky or metastatic tumors were not obtained, likely because tumor-specific T-cells travel poorly to tumor sites and because neuroblastomas are immunosuppressive.