Correlative Studies for Protocol #14-C-0059: T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Patients with GD2+ Solid Tumors, a Collaboration with CIMAC-CIDC

This study is a retrospective correlative analysis of immune cell phenotypes in samples from a Phase I clinical trial (NCT02107963) of GD2 CAR-T cells (GD2-CAR.OX40.28.z.iC9) in children and young adults with osteosarcoma and neuroblastoma. The study was a 3+3 dose-escalation study with four dose levels (1 x 10(5) transduced T cells/kg; 1 x 10⁶ transduced T cells/kg; 3 x 10⁶ transduced T cells/kg; and 1 x 10⁷ transduced T cells/kg). Apheresis and final manufactured GD2 CAR-T product samples were analyzed by bulk RNA sequencing and ATAC sequencing. The patients were stratified into good CAR-T expanders (peak CAR-T expansion >1000 GD2 CAR copies/100ng DNA) and poor CAR-T expansion (peak CAR-T expansion <1000 GD2 CAR copies/100ng DNA). The principal findings of the study are:

• Increased naïve T cell subsets in baseline apheresis are associated with patients who experienced good CAR T cell expansion
• A T cell exhaustion signature was observed in the manufactured GD2 CAR-T product and may have contributed to lack of efficacy observed in this trial
• Increased myeloid-derived suppressor cell (MDSC) signatures were observed in patients with poor CAR-T expansion
• CAR-T product in good expanders displayed increased AP-1 factor transcription factor motifs, such as BATF, JUN, and FOS

Data provided in dbGaP for this study include:

• Bulk RNA-Seq data for 11 pre-treatment peripheral blood and 11 GD2 CAR-T product from 14 patients.
• ATAC sequencing of 22 peripheral blood samples and 5 GD2 CAR-T products from 14 patients.

• Type: Clinical Cohort
• Archiver: The database of Genotypes and Phenotypes (dbGaP)