Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy

• Published in: Clinical immunology (Orlando, Fla.) Vol. 138; no. 3; pp. 255 - 265
• Main Authors: Yamasaki, Kazuki, Horiguchi, Shigetoshi, Kurosaki, Motoyoshi, Kunii, Naoki, Nagato, Kaoru, Hanaoka, Hideki, Shimizu, Naomi, Ueno, Naoyuki, Yamamoto, Seiji, Taniguchi, Masaru, Motohashi, Shinichiro, Nakayama, Toshinori, Okamoto, Yoshitaka
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2011; Elsevier
• Subjects: Aged; Allergy and Immunology; Antigen-Presenting Cells - immunology; Antineoplastic Protocols; Biological and medical sciences; Combined Modality Therapy; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Galactosylceramides - immunology; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - surgery; Head and Neck Neoplasms - therapy; Human; Humans; Immunotherapy, Adoptive; Male; Middle Aged; Natural Killer T-Cells - immunology; Neoplasms, Squamous Cell - immunology; Neoplasms, Squamous Cell - surgery; Neoplasms, Squamous Cell - therapy; NKT cell; Treatment Outcome; Tumor immunity; Human; SD; PR; Tumor immunity; HNSCC; NKT cell; αGalCer; DC; stable disease; α-galactosylceramide; partial response; dendritic cell; head and neck squamous cell carcinoma; Immune response; Natural killer T cell; Targeting; Induction; Cellular immunity; Malignant tumor; Cell immunotherapy; Tissue; Immunology; Adoptive immunization; Tumor cell; Cancer
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2010.11.014

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.