Dr. Posey of the University of Pennsylvania is developing a novel CAR-T cell therapy that selectively targets a cell surface protein (antigen) found only in neuroblastoma. Neuroblastoma is a devastating pediatric solid tumor that represents eight to 10 percent of all childhood cancer diagnoses each year. To date, there are no curative treatment options. In 2015, an antibody that targets an antigen on cancer cells called GD2 was approved for treatment of neuroblastoma patients and currently shows a 20 percent increase in 2-year event free survival over standard of care. Cellular immunotherapies, including chimeric antigen receptor (CAR) T-cells that target GD2, may further increase survival and are under development for use in neuroblastoma but are known to induce severe toxicities.
Due to treatment-related adverse events associated with anti-GD2 CAR T-cells, Dr. Posey aims to identify a novel immunotherapy strategy to treat neuroblastoma. Dr. Posey has proposed the use of poly-sialic acid (polySia) as a target for cellular immunotherapy. Because polySia is absent in normal tissue but expressed in neuroblastoma, is correlated with poor prognosis, and promotes tumor cell dissemination, invasion, and metastasis, Dr. Posey anticipates that it will serve as a more specific tumor-targeting agent than GD2; therefore, Dr. Posey will design and develop CAR T-cells to seek out polySia with the expectation that they will result in limited toxicity to surrounding tissue. Once he has generated the polySia CAR T-cells, Dr. Posey will test the anti-tumor effects and safety of the therapy in mouse models of neuroblastoma. Dr. Posey began his work in July of 2018. His goal is to translate this work to pediatric clinical trials within three to four years.