krn-7000 and Head-and-Neck-Neoplasms

Topics: Adjuvants, Immunologic; Animals; CD40 Antigens; CD40 Ligand; Cytokines; Dendritic Cells; Galactosylceramides; Head and Neck Neoplasms; Humans; Immunotherapy; Lung Neoplasms; Natural Killer T-Cells; Receptors, Antigen, T-Cell; Translational Research, Biomedical

Antigen-presenting cells (APCs) play a crucial role in the induction of immune responses. However, the optimal administration route of tumor-specific APCs for inducing effective immunological responses via cancer immunotherapy remains to be elucidated. Human NKT cells are known to have strong anti-tumor activities and are activated by the specific ligand, namely, α-galactosylceramide (αGalCer).. Seventeen patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in this study. Patients received an injection of αGalCer-pulsed APCs into the nasal, or the oral floor submucosa. Then total body image and single photon emission computed tomography (SPECT) images were examined. The immunological responses including the number of peripheral blood NKT cells, anti-tumor activities and the CD4(+) CD25(high) Foxp3(+) T cells (Tregs) induced following APCs were also compared.. APCs injected into the nasal submucosa quickly migrated to the lateral lymph nodes and those injected into the oral floor submucosa dominantly migrated to the submandibular nodes rather than the lateral lymph nodes. An increase in the absolute number of NKT cells and the IFN-γ producing cells was observed in peripheral blood after injection of the APCs into the nasal submucosa, however, these anti-tumor activities were not detected and the increased frequency of Treg cells were observed after administration into oral floor.. These results indicate that a different administration route of APCs has the potential to bring a different immunological reaction. The submucosal administration of αGalCer into the oral submucosa tends to induce immunological suppression.

Topics: Administration, Mucosal; Administration, Oral; Adult; Aged; Aged, 80 and over; Antigen-Presenting Cells; Carcinoma, Squamous Cell; CD4 Antigens; Cell Movement; Female; Galactosylceramides; Head and Neck Neoplasms; Humans; Ligands; Male; Middle Aged; Mouth Mucosa; Nasal Mucosa; Staining and Labeling; Treatment Outcome

Vα24 natural killer T (NKT) cells have potent anti-tumor activity. We performed a phase II clinical study in patients with head and neck squamous cell carcinoma (HNSCC) using ex vivo expanded Vα24 NKT cells and α-galactosylceramide (αGalCer; KRN7000)-pulsed antigen-presenting cells (APCs) to investigate the efficacy and induction of NKT cell-specific immune responses. The subjects were 10 patients with locally recurrent and operable HNSCC. One course of nasal submucosal administration of αGalCer-pulsed APCs and intra-arterial infusion of activated NKT cells via tumor-feeding arteries was given before salvage surgery. Anti-tumor effects, NKT cell-specific immune responses in extirpated cancer tissue and peripheral blood, safety, and pathological effects were evaluated. Five cases achieved objective tumor regression. The number of NKT cells increased in cancer tissues in 7 cases and was associated with tumor regression. The combination therapy induced NKT cell-specific immune responses in cancer tissues that were associated with beneficial clinical effects.

Topics: Aged; Antigen-Presenting Cells; Antineoplastic Protocols; Combined Modality Therapy; Female; Galactosylceramides; Head and Neck Neoplasms; Humans; Immunotherapy, Adoptive; Male; Middle Aged; Natural Killer T-Cells; Neoplasms, Squamous Cell; Treatment Outcome

Human Valpha24 natural killer T (NKT) cells are activated by the specific ligand, alpha-galactosylceramide (alpha-GalCer), in a CD1d-dependent manner. Potent anti-tumor activity of activated NKT cells has been previously demonstrated.. We conducted a phase I study with alpha-GalCer-pulsed antigen presenting cells (APCs) administered in the nasal submucosa of patients with head and neck cancer, and evaluated the safety and feasibility of such a treatment. Nine patients with unresectable or recurrent head and neck cancer received two treatments 1 week apart, of 1 x 10(8) of alpha-GalCer-pulsed autologous APCs into the nasal submucosa.. During the clinical study period, no serious adverse events (Common Terminology Criteria for Adverse Events version 3.0 greater than grade 3) were observed. After the first and the second administration of alpha-GalCer-pulsed APCs, an increased number of NKT cells was observed in four patients and enhanced natural killer activity was detected in the peripheral blood of eight patients.. The administration of alpha-GalCer-pulsed APCs into the nasal submucosa was found to be safe and induce anti-tumor activity in some patients.

Topics: Adult; Aged; Aged, 80 and over; Antigen-Presenting Cells; Cells, Cultured; Female; Galactosylceramides; Head and Neck Neoplasms; Humans; Immunotherapy; Interferon-gamma; Killer Cells, Natural; Leukocytes, Mononuclear; Lymphocyte Transfusion; Male; Middle Aged; Nasal Mucosa; Phenotype; Recurrence; Tomography, X-Ray Computed; Treatment Outcome