Review Article

Invariant NKT Cells as Novel Targets for Immunotherapy in Solid Tumors

Table 1

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

TumorNumber of patientsTreatment regimenSummary of study resultsReference

(A) Direct α-galactosylceramide injection

 Solid tumors24α-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 cancer6Vα24NKT 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 cancer11α-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 cancer9α-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 cancer23α-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 cancer4α-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 cancer8In 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]