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A Phase I Study of In vitro Expanded Natural Killer T Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer

Authors' Affiliations: Departments of ¹ Immunology, ² Thoracic Surgery, and ³ Otorhinolaryngology, Graduate School of Medicine, Chiba University; ⁴ Clinical Research Center; and ⁵ Division of Blood Transfusion, Chiba University Hospital, Chiba, Japan; and ⁶ Laboratory of Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, 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 V24 natural killer T (V24 NKT) cells bearing an invariant V24JQ antigen receptor are activated by a glicolipid ligand -galactosylceramide (GalCer; KRN7000) in a CD1d-dependent manner. The human V24 NKT cells activated with GalCer and interleukin-2 have been shown to produce large amounts of cytokines, such as IFN-, and also exerting a potent killing activity against various tumor cell lines. We did a phase I study with autologous activated V24 NKT cell therapy.

Experimental Design: Patients with advanced or recurrent non–small cell lung cancer received i.v. injections of activated V24 NKT cells (level 1: 1 x 10⁷/m² and level 2: 5 x 10⁷/m²) to test the safety, feasibility, and clinical response of this therapeutic strategy. Immunomonitoring was also done in all cases.

Results: Six patients were enrolled in this study. No severe adverse events were observed during this study in any patients. After the first and second injection of activated V24 NKT cells, an increased number of peripheral blood V24 NKT cells was observed in two of three cases receiving a level 2 dose of activated V24 NKT cells. The number of IFN--producing cells in peripheral blood mononuclear cells increased after the administration of activated V24 NKT cells in all three cases receiving the level 2 dose. No patient was found to meet the criteria for either a partial or a complete response.

Conclusions: The clinical trial with activated V24 NKT cell administration was well tolerated and carried out safely with minor adverse events even in patients with advanced diseases.

Commentary

Natural Killer T Cell–Based Cancer Immunotherapy

Hans J.J. van der Vliet, Steven P. Balk, and Mark A. Exley
Clin. Cancer Res. 2006 12: 5921-5923. [Full Text] [PDF]

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