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Nasal submucosal administration of antigen-presenting cells induces effective immunological responses in cancer
Yoshitaka Okamoto1, Akira Fujikawa, Motoyoshi Kurosaki
1Department 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
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.
Insights
Nasal submucosal injection of alpha-galactosylceramide (αGelCer)-pulsed dendritic cells (DCs) is safe and effective for head and neck cancer. This immunotherapy boosts NKT cell activity and shows promising clinical effects.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Human Natural Killer T (NKT) cells possess potent antitumor activity.
- NKT cell activation is triggered by specific ligands, such as alpha-galactosylceramide (αGelCer).
Purpose of the Study:
- To investigate the migration patterns and immune responses of αGelCer-pulsed dendritic cells (DCs) administered via different routes.
- To evaluate the safety and feasibility of nasal submucosal administration of αGelCer-pulsed DCs in patients with head and neck cancer.
Main Methods:
- αGelCer-pulsed DCs were administered via nasal submucosa, and their migration patterns were tracked.
- Immune responses, including NKT cell numbers and IFN-γ production, were monitored in peripheral blood.
- A Phase I clinical trial was conducted to assess safety and feasibility in head and neck cancer patients.
Main Results:
- Nasal submucosal injection of DCs led to rapid migration to lateral neck lymph nodes.
- Significant increases in NKT cells and IFN-γ-producing cells were observed in peripheral blood.
- Nasal submucosal administration of αGelCer-pulsed DCs was found to be safe, feasible, and elicited notable immune responses and clinical benefits in head and neck cancer patients.
Conclusions:
- Nasal submucosal administration of αGelCer-pulsed DCs represents a safe and potentially effective immunotherapy for head and neck cancer.
- This approach can induce significant antitumor immunity and clinical benefits, warranting further investigation.
- NKT cell-based cancer immunotherapy holds promise for managing head and neck cancers.
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