RT Journal Article
SR Electronic
T1 A Phase I Study of α-Galactosylceramide (KRN7000)–Pulsed Dendritic Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 1910
OP 1917
DO 10.1158/1078-0432.CCR-04-1453
VO 11
IS 5
A1 Ishikawa, Aki
A1 Motohashi, Shinichiro
A1 Ishikawa, Eiichi
A1 Fuchida, Hiroki
A1 Higashino, Kazuko
A1 Otsuji, Mizuto
A1 Iizasa, Toshihiko
A1 Nakayama, Toshinori
A1 Taniguchi, Masaru
A1 Fujisawa, Takehiko
YR 2005
UL http://clincancerres.aacrjournals.org/content/11/5/1910.abstract
AB Purpose: Human Vα24 natural killer T (NKT) cells bearing an invariant Vα24JαQ antigen receptor, the counterpart of murine Vα14 NKT cells, are activated by a specific ligand, α-galactosylceramide (αGalCer, KRN7000), in a CD1d-dependent manner. I.v. administration of αGalCer-pulsed dendritic cells (DC) induces significant activation and expansion of Vα14 NKT cells in the lung and resulting potent antitumor activities in mouse tumor metastatic models. We did a phase I dose escalation study with αGalCer-pulsed DCs in lung cancer patients. Experimental Design: Patients with advanced non–small cell lung cancer or recurrent lung cancer received i.v. injections of αGalCer-pulsed DCs (level 1: 5 × 107/m2; level 2: 2.5 × 108/m2; and level 3: 1 × 109/m2) to test the safety, feasibility, and clinical response. Immunomonitoring was also done in all completed cases. Results: Eleven patients were enrolled in this study. No severe adverse events were observed during this study in any patient. After the first and second injection of αGalCer-pulsed DCs, dramatic increase in peripheral blood Vα24 NKT cells was observed in one case and significant responses were seen in two cases receiving the level 3 dose. No patient was found to meet the criteria for partial or complete responses, whereas two cases in the level 3 group remained unchanged for more than a year with good quality of life. Conclusions: In this clinical trial, αGalCer-pulsed DC administration was well tolerated and could be safely done even in patients with advanced disease.