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Clin Cancer Res. 2005 Mar 1;11(5):1910-7.

A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer.

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  • 1Department of Immunology and Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Abstract

PURPOSE:

Human Valpha24 natural killer T (NKT) cells bearing an invariant Valpha24JalphaQ antigen receptor, the counterpart of murine Valpha14 NKT cells, are activated by a specific ligand, alpha-galactosylceramide (alphaGalCer, KRN7000), in a CD1d-dependent manner. I.v. administration of alphaGalCer-pulsed dendritic cells (DC) induces significant activation and expansion of Valpha14 NKT cells in the lung and resulting potent antitumor activities in mouse tumor metastatic models. We did a phase I dose escalation study with alphaGalCer-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 alphaGalCer-pulsed DCs (level 1: 5 x 10(7)/m(2); level 2: 2.5 x 10(8)/m(2); and level 3: 1 x 10(9)/m(2)) 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 alphaGalCer-pulsed DCs, dramatic increase in peripheral blood Valpha24 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, alphaGalCer-pulsed DC administration was well tolerated and could be safely done even in patients with advanced disease.

PMID:
15756017
[PubMed - indexed for MEDLINE]
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