PT  - JOURNAL ARTICLE
AU  - Ishikawa, Aki
AU  - Motohashi, Shinichiro
AU  - Ishikawa, Eiichi
AU  - Fuchida, Hiroki
AU  - Higashino, Kazuko
AU  - Otsuji, Mizuto
AU  - Iizasa, Toshihiko
AU  - Nakayama, Toshinori
AU  - Taniguchi, Masaru
AU  - Fujisawa, Takehiko
TI  - A Phase I Study of α-Galactosylceramide (KRN7000)–Pulsed Dendritic Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer
AID  - 10.1158/1078-0432.CCR-04-1453
DP  - 2005 Mar 01
TA  - Clinical Cancer Research
PG  - 1910--1917
VI  - 11
IP  - 5
4099  - http://clincancerres.aacrjournals.org/content/11/5/1910.short
4100  - http://clincancerres.aacrjournals.org/content/11/5/1910.full
SO  - Clin Cancer Res2005 Mar 01; 11
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.