[Frontiers in Bioscience S1, 108-116, June 1, 2009]

Natural killer T cell-mediated immunotherapy for malignant diseases

Shinichiro Motohashi1,2, Toshinori Nakayama1

1 Department of Immunology and 2 Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Properties of human Valpha24 NKT cells
3.1. Functional monitoring of Valpha24 NKT cells
3.2. Vaipha24 NKT cells in cancer bearing condition
4. Clinical study of NKT cell-based immunotherapy
4.1. Active immunotherapy
4.1.1. Direct administration of alpha-GalCer
4.1.2. Dendritic cell therapy pulsed with alpha-GalCer
4.2. Adoptive immunotherapy
5. Perspective
6. Acknowledgements
7. References

1. ABSTRACT

Human invariant Valpha24 Natural Killer T (NKT) cells are unique lymphocyte subsets, characterized by an invariant T-cell receptor Valpha24 chain paired with Vbeta11. Recent findings have highlighted the role of NKT cells in tumor immunity. Valpha24 NKT cells are activated by a specific glycolipid ligand, alpha-Galactosylceramide and rapidly produce high levels of cytokines upon stimulation, thereby modulating other immune cells such as NK cells antigen-specific CD4+ and CD8+ T cells and dendritic cells. Abnormalities in the numbers and functions of Valpha24 NKT cells have been observed in patients with various malignant diseases. Therefore, therapeutic strategies have recently focused on the reconstitution of an adequate number of functionally sufficient Valpha24 NKT cells which is thought to be logical and reasonable for cancer treatment. The quantitative alteration and functional impairment of circulating Valpha24 NKT cells are herein reviewed in various cancer-bearing patients and the progress to date in the clinical applications of NKT cell-based tumor immunotherapy is summarized.