Combination therapy of in vitro‐expanded natural killer T cells and α‐galactosylceramide‐pulsed antigen‐presenting cells in patients with recurrent head and neck carcinoma
Open Access
- 20 May 2009
- journal article
- Published by Wiley in Cancer Science
- Vol. 100 (6), 1092-1098
- https://doi.org/10.1111/j.1349-7006.2009.01135.x
Abstract
The aim of this clinical trial was to investigate the feasibility of intra-arterial infusion of in vitro-expanded Vα24 natural killer T (NKT) cells combined with submucosal injection of α-galactosylceramide (KRN7000; αGalCer)-pulsed antigen-presenting cells (APC). A phase I clinical study was carried out in patients with head and neck squamous cell carcinoma (HNSCC). Patients with locally recurrent HNSCC refractory to standard therapy were eligible. Eight patients received super-selective transcatheter intra-arterial infusion of activated Vα24 NKT cells into tumor-feeding arteries and nasal submucosal injections of αGalCer-pulsed APC twice with a 1-week interval. Vα24 NKT cell-specific immune responses, safety, and antitumor effects were evaluated. The number of Vα24 NKT cells and interferon-γ-producing cells in peripheral blood mononuclear cells increased in seven out of eight patients enrolled. Grade 3 toxicity with a pharyngocutaneous fistula related to local tumor reduction was observed in one patient and mild adverse events with grade 1–2 symptoms occurred in seven patients. Regarding the clinical responses, three cases exhibited a partial but significant response, four were classified as stable disease, and one patient continued to develop progressive disease. The use of the intra-arterial infusion of activated Vα24 NKT cells and the submucosal injection of αGalCer-pulsed APC has been shown to induce significant antitumor immunity and had beneficial clinical effects in the management of advanced HNSCC. The use of such therapeutic modalities may be helpful in the management of tumors and therefore needs to be explored in further detail. The clinical trial registration number was UMIN000000722. (Cancer Sci 2009; 100: 1092–1098)Keywords
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