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.