title: Combination therapy of in vitro-expanded natural killer T cells and alpha-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma.
abstract: The aim of this clinical trial was to investigate the feasibility of intra-arterial infusion of in vitro-expanded Valpha24 natural killer T (NKT) cells combined with submucosal injection of alpha-galactosylceramide (KRN7000; alphaGalCer)-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 Valpha24 NKT cells into tumor-feeding arteries and nasal submucosal injections of alphaGalCer-pulsed APC twice with a 1-week interval. Valpha24 NKT cell-specific immune responses, safety, and antitumor effects were evaluated. The number of Valpha24 NKT cells and interferon-gamma-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 Valpha24 NKT cells and the submucosal injection of alphaGalCer-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.
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kunii
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Heizaburo
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Ueno
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Daiju
authors.initials: D
authors.lastname: Sakurai
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000276:immunology* / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000532:radiotherapy / Q000601:surgery; D018579:Patient Selection
chemical_list: D005699:Galactosylceramides