TRAC-CAR T cells and low-dose RPT in localized neuroblastoma
Sodji QH, Shea A, Cappabianca D, et al. Low-Dose Radiation by Radiopharmaceutical Therapy Enhances GD2 TRAC-CAR T Cell Efficacy in Localized Neuroblastoma. Science Advances. 2025; 11 (23) (doi: 10.1126/sciadv.adu4417).
Chimeric antigen receptor (CAR) T-cell efficacy against solid tumors has room for improvement, and researchers are exploring low-dose radiation as one possible pathway to better outcomes. Their localized neuroblastoma model used the radiopharmaceutical therapy (RPT) agent 177Lu-NM600 to irradiate tumors 9 days ahead of CAR-T cell infusion. The CRISPR-edited GD2 TRAC-CAR T cells responded to the low-dose radiation by secreting more perforin, granzyme B, tumor necrosis factor α, and interleukin-7 but less transforming growth factor β1. An additional effect was death receptor Fas up-regulation on neuroblastoma, which potentially mediated cytotoxic behavior independent of CARs.