Dr. Avery Posey – University of Pennsylvania
CureSearch Young Investigator Award: 2018-2020
Project Title: Polysialic acid-specific CAR T-cells for the treatment of neuroblastoma
Project Overview: Neuroblastoma is a devastating pediatric solid tumor that is diagnosed in nearly 700 children each year. Neuroblastoma is most frequently diagnosed in very young children, by the age of 5 and the median age of diagnosis is 18 months. Though general 5-year survival for neuroblastoma is 80%, in patients with high-risk disease, survival is approximately 50%. While current immunotherapy options for neuroblastoma result in an increase in survival, treatment-related side-effects, including severe pain, limit how much the therapy can be used. Such side-effects demonstrate the necessity of new therapies that are both effective and safe.
Dr. Posey aims to reduce toxicity and increase efficacy of neuroblastoma treatment by training immune cells to seek and destroy neuroblastoma while ignoring the normal cells of the body. A novel target for immunotherapy in neuroblastoma is poly-sialic acid (polySia). PolySia is absent in normal tissues post-embryonic development and reemerges during tumor development and progression. High expression of polySia is correlated with poor prognosis. PolySia expression increases tumor migration and proliferation in vitro and the promotion of tumor cell dissemination, invasion, and metastasis in vivo. Dr. Posey will develop a novel CAR T-cell therapy targeting polySia for the treatment of pediatric neuroblastoma.
Project Update: As of June 2020, Dr. Posey has developed four CARTs. He has identified a lead construct that induces potent cytotoxicity against neuroblastoma. With an optimized CAR molecule, he has begun to evaluate the anti-tumor efficacy of this therapy in xenograft mouse models.