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Cancer Therapy: Clinical |
-Galactosylceramide (KRN7000)–Pulsed Dendritic Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer
1 Department of Immunology and 2 Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan and 3 Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
Requests for reprints: Toshinori Nakayama, Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Phone: 81-43-226-2186; Fax: 81-43-227-1498; E-mail: tnakayama{at}faculty.chiba-u.jp.
Purpose: Human V
24 natural killer T (NKT) cells bearing an invariant V24JQ antigen receptor, the counterpart of murine V14 NKT cells, are activated by a specific ligand, -galactosylceramide (GalCer, KRN7000), in a CD1d-dependent manner. I.v. administration of GalCer-pulsed dendritic cells (DC) induces significant activation and expansion of V14 NKT cells in the lung and resulting potent antitumor activities in mouse tumor metastatic models. We did a phase I dose escalation study with GalCer-pulsed DCs in lung cancer patients.
Experimental Design: Patients with advanced non–small cell lung cancer or recurrent lung cancer received i.v. injections of GalCer-pulsed DCs (level 1: 5 x 107/m2; level 2: 2.5 x 108/m2; and level 3: 1 x 109/m2) to test the safety, feasibility, and clinical response. Immunomonitoring was also done in all completed cases.
Results: Eleven patients were enrolled in this study. No severe adverse events were observed during this study in any patient. After the first and second injection of GalCer-pulsed DCs, dramatic increase in peripheral blood V24 NKT cells was observed in one case and significant responses were seen in two cases receiving the level 3 dose. No patient was found to meet the criteria for partial or complete responses, whereas two cases in the level 3 group remained unchanged for more than a year with good quality of life.
Conclusions: In this clinical trial, GalCer-pulsed DC administration was well tolerated and could be safely done even in patients with advanced disease.
Key Words: NKT cell • clinical trial • immunotherapy
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