PHOX2B PC-CAR T Cells for Relapsed Neuroblastoma

Neuroblastoma is a tumor of childhood arising from neural crest-derived cells of the developing sympathetic nervous system. While neuroblastomas in young infants often spontaneously regress, children diagnosed with advanced disease after 18 months of age experience poor overall survival despite intensive therapy. Neuroblastoma is a heterogenous disease, but approximately 50% of patients have a "high-risk" clinical phenotype defined by well-established clinical signs and molecular biomarkers. Over 50% of patients ultimately relapse and survivors are often burdened with significant long-term therapy related morbidities. There is no known cure for patients with relapsed high-risk neuroblastoma. PHOX2B as a therapeutic target for neuroblastoma Paired like homeobox 2B (PHOX2B) is a homeodomain transcription factor that promotes differentiation of neural crest cell derived sympathetic nervous system precursor cells. The PHOX2B protein is so specifically expressed in neuroblastoma that it is used an immunohistochemical confirmation of diagnosis. While PHOX2B is expressed during fetal development, PHOX2B expression is silenced in the vast majority of normal tissues after birth. To therapeutically leverage this differential expression, an HLA restricted PHOX2B PC-CAR T cell was developed and showed potent inhibition of the growth of neuroblastoma patient-derived xenografts. This investigation will be a single institution, open-label first in human, dose escalation and expansion study designed to assess the safety, tolerability, and manufacturing feasibility of PHOX2B- PC CAR T Cells.