Immune Correlates of GD2 CAR T Cell Expansion in Pediatric Osteosarcoma and Neuroblastoma Patients

→ Speaker: Sneha Ramakrishna, MD, Center for Cancer Cell Therapy, Stanford University School of Medicine

Ramakrishna conducted a phase I trial (NCT02107963) to determine the feasibility of production and safety of administering escalating doses of GD2.Ox40.CD28.z chimeric antigen receptor T cells (GD2-CAR T) in children and young adults with neuroblastoma and osteosarcoma. She explains the robust GD2-CAR T expansion observed in half of the patients but limited persistence in all patients.

With inadequate expansion a known barrier to CAR T efficacy, the team comprehensively evaluated phenotypic immune profiles of patient apheresis samples to identify determinants of CAR T expansion. Using CyTOF®, they found GD2-CAR T expansion to be significantly correlated with several T cell markers, including a larger baseline naive and central memory T cell pool, and unique myeloid populations at baseline that were negatively correlated with CAR T expansion. The findings highlight the potential to define and apply molecular signatures as biomarkers and prognostic indicators of CAR T expansion, with promise for advancing immunotherapies for solid tumor patients in the future.