Translational research in patients with lung cancer--clinical application of NKT cell immunotherapy

摘要

Human V alpha 24 natural killer T (NKT) cells bearing an invariant V alpha 24 J alpha Q antigen receptor, the counterpart of murine V alpha 14 NKT cells, are activated by a specific ligand, alpha-galactosylceramide (alpha GalCer; KRN 7000), in a CD 1 d-dependent manner. Previous findings showed that alpha GalCer-pulsed dendritic cells (DCs) exerted a strong antitumor activity in the mouse tumor metastatic models, and intravenous administration of alpha GalCer-pulsed DCs led to V alpha 14 NKT cell expansion in the lung. With these results, we performed a phase I dose escalation study of alpha GalCer-pulsed DCs treatment in patients with lung cancer. Patients with advanced non-small cell lung cancer or recurrent lung cancer received intravenous injection of alpha GalCer pulsed dendritic cell immune therapy to test the safety, feasibility, and clinical response. Immunomonitoring was also performed in all completed cases. Eleven patients were enrolled in this study, None of whom experienced severe adverse events. Peripheral blood V alpha 24 NKT cells dramatically increased after the first and second injection of alpha GalCer pulsed DCs in one patient of level 3. The clinical trial of alpha GalCer-pulsed DCs administration is well tolerated,and this therapy has been carried out safely. To obtain more conclusive findings about immune responses and antitumor responses, a phase I-II study with greater numbers of patients is ongoing.