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Tumor | Number of patients | Treatment regimen | Summary of study results | Reference |
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(A) Direct α-galactosylceramide injection |
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Solid tumors | 24 | α-Galactosylceramide i.v. (40–4800 μg/m2) | (1) No dose-limiting toxicity (2) Increase serum TNF-α and GM-CSF in 5 of 24 patients (3) Response dependent on pre-existing number of NKT cells which were significantly lower in cancer patients | Giaccone et al., 2002 [89] |
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(B) Infusion of ex vivo expanded NKT cells |
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Nonsmall cell lung cancer | 6 | Vα24NKT cells restimulated with α-galactosylceramide-pulsed PBMCs | (1) No adverse effects (2) Highest dose induced expansion of NKT cells (in 2 of 3 patients) and IFN-γ producing cells (in 3 of 3 patients) | Motohashi et al., 2006 [90] |
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(C) Ex vivo generated DC loaded with α-GalCer |
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Nonsmall cell lung cancer | 11 | α-Galactosylceramide-pulsed dendritic cells | (1) No severe toxicities (2) Increase NKT cells in 1 of 11 patients (3) No partial or complete response seen | Ishikawa et al., 2005 [91] |
Head and neck cancer | 9 | α-Galactosylceramide-pulsed APC | (1) No serious toxicities (2) Increase NKT cells in 4/9 patients (3) Increase NK activity in 8/9 patients | Uchida et al., 2008 [92] |
Nonsmall cell lung cancer | 23 | α-Galactosylceramide-pulsed PBMC cultured with IL-2/GM-CSF | (1) No severe toxicities (2) Stable disease in 5 (3) Increased IFN response correlated with survival | Motohashi et al., 2009 [93] |
Nonsmall cell lung cancer | 4 | α-Galactosylceramide-pulsed APC | (1) Increase in NKT cells in lung tumors (2) Highest IFN-γ production following in vitro restimulation of TILs with α-galactosylceramide |
Nagato, K et al 2012 [94]
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(D) Combination strategies |
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Head and neck squamous cell cancer | 8 | In vitro expanded NKT + α-galactosylceramide-pulsed APC | (1) Transient and mild adverse effects (2) Increased NKT cells and IFN-γ secretion in 7 of 8 patients (3) Partial response in 3 patients, stable disease in 4, progressive disease in 1 |
Kunii, N et al, 2009 [95]
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