title: Nasal submucosal administration of antigen-presenting cells induces effective immunological responses in cancer immunotherapy.
abstract: Human NKT cells are known to have strong antitumor activities and to be activated by specific ligand, α-galactosylceramide (αGelCer). We examined the migration pattern of αGalCer-pulsed DCs and the immune responses after administration by different routes. DCs injected into nasal submucosa quickly migrated to the lateral neck lymph rather than the lateral lymph nodes. The absolute number of NKT cells and the IFN-γ-producing cells increased in peripheral blood after injection of the DCs into nasal submucosa. We conducted a phase I study with αGalCer-pulsed DCs administered in nasal submucosa of patients with head and neck cancer, and evaluated safety and feasibility. The results showed that nasal submucosal administration of α-GalCer-pulsed DCs was safe and a smaller number of these DCs could exhibit significant immune responses and some positive clinical effects. In additional study, the use of the intra-arterial infusion of activated NKT cells and the submucosal injection of α-GalCer-pulsed DCs has been shown to induce significant antitumor immunity and had beneficial clinical effects in the management of advanced head and neck squamous cell carcinoma. The NKT cell-based cancer immunotherapy may be helpful in management of head and neck cancer and needs to be explored in further detail.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University Hospital, and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. yokamoto@faculty.chiba-u.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Fujikawa
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Daijyu
authors.initials: D
authors.lastname: Sakurai
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000281:Administration, Intranasal; D000938:Antigen-Presenting Cells; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007167:Immunotherapy / Q000379:methods*; D009367:Neoplasm Staging; D020551:Pulse Therapy, Drug; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage / Q000276:immunology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D011948:Receptors, Antigen, T-Cell; C528689:Valpha24 protein, human