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.
PURPOSE:Human Valpha24 natural killer T (NKT) cells bearing an invariant Valpha24JalphaQ antigen receptor, the counterpart of murineValpha14 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 mousetumor metastatic models. We did a phase I dose escalation study with alphaGalCer-pulsed DCs in lung cancerpatients. 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.
Authors: Thomas H Beckham; Saeed Elojeimy; Joseph C Cheng; Lorianne S Turner; Stanley R Hoffman; James S Norris; Xiang Liu Journal: Expert Opin Ther Targets Date: 2010-05 Impact factor: 6.902