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.

Activation of invariant natural killer T cells in regional lymph nodes as new antigen-specific immunotherapy via induction of interleukin-21 and interferon-γ

“…We have reported previously that DCs isolated from PBMCs of patients with head and neck cancer migrated to CLNs after oral submucosal administration , and we showed that this treatment was safe . Simultaneous administration of an antigen with α‐GalCer‐DCs is thus an accessible way to activate iNKT cells in regional lymph nodes; however, further studies are needed to clarify the role of activated iNKT cells in regional lymph nodes in treatment of AR.…”

Targeting Sphingolipids for Cancer Therapy

“…This activation is associated with increased serum levels of cytokines that stimulate the growth and function of T cells [IL-12 ( 150 , 175 ) and IL-2 receptors ( 175 )] and other factors that enhance natural killer cell activity (i.e., interferon gamma [IFN-γ] ( 150 , 155 , 156 , 158 , 161 , 163 , 172 ), CD16 ( 175 ), and tumor necrosis factor α [TNF-α]) and immune cell maturation (GMCSF) ( 164 ). In eleven out of twelve completed phase I-II clinical trials, tumor regression, stable disease, partial response or increased median survival time were observed in a subgroup of patients ( 153 , 157 , 159 , 160 , 162 – 169 ). These promising clinical findings are associated with the activation of natural killer cells, cytotoxic CD8+ T cells and CD4+ T cells, which are the most relevant immune responses to cancer ( 230 ).…”

Immunotherapy for Head and Neck Cancer Patients: Shifting the Balance

“…The other fi ve patients had stable disease. In a recent trial, 17 HNSCC patients were enrolled in a study comparing APC administration via the nasal mucosa with administration via the oral mucosa [96]. An increase in activated NKT cells was detected in patients receiving α-GalCer-loaded APCs administrated via the nasal mucosa.…”