NKT cells co-expressing a GD2-specific chimeric antigen receptor and IL-15 mediate regression of refractory metastatic neuroblastoma

Despite remarkable progress in B cell malignancies, T cells expressing chimeric antigen receptors (CARs) remain ineffective in solid tumors in part because T cells do not traffic effectively to or survive in tumor tissues. We engineered Vα24-invariant natural killer T cells (NKTs), which intrinsically home to tumor sites, to co-express a GD2-specific CAR with interleukin (IL)15 and evaluated their therapeutic efficacy in children with relapsed/resistant neuroblastoma (NB)(NCT03294954). The first three patients received a single infusion of 3x10e6 autologous CAR-NKTs per square meter of body surface area and tolerated the treatment well. CAR-NKTs expanded in vivo, localized to the tumor, and in one patient induced a near-complete regression of bone metastatic lesions. Single-cell RNA-seq of pre-infusion CAR-NKTs from three cancer patients.