Phase II study of alpha-galactosylceramide-pulsed antigen-presenting cells in patients with advanced or recurrent non-small cell lung cancer

Background Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to specific glycolipid antigens such as alpha -galactosylceramide (alpha GalCer) presented by CD1d-expressing antigen-presenting cells (APCs), thus orchestrating other immune cells to fight tumors. Because of their ability to induce strong antitumor responses activated by alpha GalCer, iNKT cells have been studied for their application in cancer immunotherapy. In our previous phase I/II trial in non-small cell lung cancer (NSCLC) patients who had completed the standard treatment, we showed a relatively long median survival time without severe treatment-related adverse events. Based on these results, we performed a phase II trial to evaluate clinical responses, safety profiles and immune responses as a second-line treatment for advanced NSCLC. Methods Patients with advanced or recurrent NSCLC refractory to first-line chemotherapy were eligible. alpha GalCer-pulsed APCs were intravenously administered four times. Overall survival time was evaluated as the primary endpoint. The safety profile and immune responses after APC injection were also monitored. This study was an open label, single-arm, phase II clinical trial performed at Chiba University Hospital, Japan. Results Thirty-five patients were enrolled in this study, of which 32 (91.4%) completed the trial. No severe adverse events related to the treatment were observed. The estimated median survival time of the 35 cases was 21.9 months (95% CI, 14.8 to 26.0). One case (2.9%) showed a partial response, 14 cases (40.0%) remained as stable disease, and 19 cases (54.3%) were evaluated as progressive disease. The geometric mean number of iNKT cells in all cases was significantly decreased and the mean numbers of natural killer (NK) cells, interferon-gamma -producing cells in response to alpha GalCer, and effector CD8+ T cells were significantly increased after the administration of alpha GalCer-pulsed APCs. Conclusions The intravenous administration of alpha GalCer-pulsed APCs was well-tolerated and was accompanied by prolonged overall survival. These results are encouraging and warrant further evaluation in a randomized phase III trial to demonstrate the survival benefit of this immunotherapy. Trial registration number UMIN000007321.