Abstract
Natural killer T (NKT) cells are characterized by the expression of an invariant Vα14Jα18 receptor that recognizes glycolipids such as α-galactosylceramide (α-GalCer) in conjunction with CD1d molecule. Functionally, NKT cells can act as innate immune cells but can also bridge the innate and acquired immune systems. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses by their production of IFN-γ, which acts on NK cells to eliminate MHC− target tumor cells and also on CD8 cytotoxic T cells to kill MHC+ tumor cells. Thus, when NKT cells are activated with α-GalCer-pulsed dendritic cells, both MHC− and MHC+ tumor cells can be effectively eliminated. Since both types of tumor cells are simultaneously present in cancer patients, NKT cells are only the cell type that can circumvent the difficult problem of eliminating them. Based on these findings, we have developed NKT-cell-targeted adjuvant cell therapies with strong anti-tumor activity in humans. However, two-thirds of patients were not eligible for this therapy because they no longer had sufficient numbers of NKT cells. To overcome the problem of the limited number of NKT cells in cancer patients, we successfully established a method to generate NKT cells with adjuvant activity from induced pluripotent stem (iPS) cells. Thus, the iPS technology has shown great promise for future cancer therapy.
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Acknowledgments
The authors are grateful to Dr. Peter Burrows for helpful comments and constructive criticisms in the preparation of the manuscript. We also grateful to Drs. Shin-ichiro Motohashi and Toshinori Nakayama at Chiba University for collaboration on the Phase I/IIa clinical studies.
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Taniguchi, M. et al. (2012). Introduction: Mechanisms of NKT-Cell-Mediated Adjuvant Activity and Function of iPS-Derived NKT Cells. In: Terabe, M., Berzofsky, J. (eds) Natural Killer T cells. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0613-6_1
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DOI: https://doi.org/10.1007/978-1-4614-0613-6_1
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