Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Vα24-invariant natural killer T (NKT) cells possess anti-tumor properties but are scarce in humans, limiting clinical use.
• Neuroblastoma is a challenging pediatric cancer, particularly in relapsed or resistant cases.

Purpose of the Study:

• To evaluate the safety and preliminary anti-tumor efficacy of autologous chimeric antigen receptor (CAR)-NKT cells engineered with interleukin-15.
• To assess immune responses in children with relapsed or resistant neuroblastoma receiving CAR-NKT cell therapy.

Main Methods:

• Phase 1 dose-escalation trial involving three pediatric patients with relapsed/resistant neuroblastoma.
• Treatment involved autologous NKT cells engineered to express a GD2-specific CAR and IL-15, administered after cyclophosphamide/fludarabine (Cy/Flu) lymphodepletion.
• Ex vivo expansion yielded highly pure NKT cells (94.7 ± 3.8%) administered at 3 × 10⁶ CAR-NKT cells/m².

Main Results:

• No dose-limiting toxicities were observed; grade 3-4 hematologic adverse events were likely due to Cy/Flu conditioning.
• CAR-NKT cells demonstrated in vivo expansion and tumor localization.
• One patient achieved an objective response, including regression of bone metastatic lesions.

Conclusions:

• Autologous CAR-NKT cells can be expanded to clinical scale and administered safely.
• The findings suggest potential for CAR-NKT cell therapy in treating pediatric neuroblastoma and other cancers.