Table 1.

Summary of NKT-based phase I/II clinical trials.

Tumor	Number of patients	Treatment regimen	Summary of study results	Reference
(A) Direct α-galactosylceramide injection
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]
(B) Infusion of ex vivo expanded NKT cells
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]
(C) Ex vivo generated DC loaded with α-GalCer
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]
(D) Combination strategies
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]