A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer.
OBJECTIVE
Human Valpha24 natural killer T (Valpha24 NKT) cells bearing an invariant Valpha24JalphaQ antigen receptor are activated by a glicolipid ligand alpha-galactosylceramide (alphaGalCer; KRN7000) in a CD1d-dependent manner. The human Valpha24 NKT cells activated with alphaGalCer and interleukin-2 have been shown to produce large amounts of cytokines, such as IFN-gamma, and also exerting a potent killing activity against various tumor cell lines. We did a phase I study with autologous activated Valpha24 NKT cell therapy.


METHODS
Patients with advanced or recurrent non-small cell lung cancer received i.v. injections of activated Valpha24 NKT cells (level 1: 1 x 10(7)/m2 and level 2: 5 x 10(7)/m2) to test the safety, feasibility, and clinical response of this therapeutic strategy. Immunomonitoring was also done in all cases.


RESULTS
Six patients were enrolled in this study. No severe adverse events were observed during this study in any patients. After the first and second injection of activated Valpha24 NKT cells, an increased number of peripheral blood Valpha24 NKT cells was observed in two of three cases receiving a level 2 dose of activated Valpha24 NKT cells. The number of IFN-gamma-producing cells in peripheral blood mononuclear cells increased after the administration of activated Valpha24 NKT cells in all three cases receiving the level 2 dose. No patient was found to meet the criteria for either a partial or a complete response.


CONCLUSIONS
The clinical trial with activated Valpha24 NKT cell administration was well tolerated and carried out safely with minor adverse events even in patients with advanced diseases.
Motohashi
Shinichiro
S
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ishikawa
Aki
A
Ishikawa
Eiichi
E
Otsuji
Mizuto
M
Iizasa
Toshihiko
T
Hanaoka
Hideki
H
Shimizu
Naomi
N
Horiguchi
Shigetoshi
S
Okamoto
Yoshitaka
Y
Fujii
Shin-ichiro
S
Taniguchi
Masaru
M
Fujisawa
Takehiko
T
Nakayama
Toshinori
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008175:Lung Neoplasms / Q000628:therapy*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion / Q000009:adverse effects*; D008875:Middle Aged; D018579:Patient Selection; D012008:Recurrence