Osteosarcoma study on dbGaP (15 participants)

phs003455 — 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 (<a href="https://clinicaltrials.gov/study/NCT02107963?term=NCT02107963">NCT02107963</a>) 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 &#x3C;1000 GD2 CAR copies/100ng DNA). The principal findings of the study are: <ul><li>Increased naïve T cell subsets in baseline apheresis are associated with patients who experienced good CAR T cell expansion </li><li>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 </li><li>Increased myeloid-derived suppressor cell (MDSC) signatures were observed in patients with poor CAR-T expansion </li><li>CAR-T product in good expanders displayed increased AP-1 factor transcription factor motifs, such as <a href="https://www.ncbi.nlm.nih.gov/gene/10538">BATF</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/3725">JUN</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/2353">FOS</a> </li></ul> Data provided in dbGaP for this study include: <ul><li>Bulk RNA-Seq data for 11 pre-treatment peripheral blood and 11 GD2 CAR-T product from 14 patients. </li><li>ATAC sequencing of 22 peripheral blood samples and 5 GD2 CAR-T products from 14 patients. </li></ul>

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