Uchida Tetsuro, Horiguchi Shigetoshi, Tanaka Yuriko, Yamamoto Heizaburo, Kunii Naoki, Motohashi Shinichiro, Taniguchi Masaru, Nakayama Toshinori, Okamoto Yoshitaka
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Cancer Immunol Immunother. 2008 Mar;57(3):337-45. doi: 10.1007/s00262-007-0373-5. Epub 2007 Aug 10.
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.
人Vα24自然杀伤T（NKT）细胞以CD1d依赖的方式被特异性配体α-半乳糖神经酰胺（α-GalCer）激活。先前已证明活化的NKT细胞具有强大的抗肿瘤活性。
我们对α-GalCer脉冲抗原呈递细胞（APC）在头颈部癌患者鼻黏膜下层给药进行了I期研究，并评估了这种治疗的安全性和可行性。9例不可切除或复发性头颈部癌患者接受了两次间隔1周的治疗，将1×10⁸个α-GalCer脉冲自体APC注入鼻黏膜下层。
在临床研究期间，未观察到严重不良事件（不良事件通用术语标准3.0版大于3级）。在首次和第二次给予α-GalCer脉冲APC后，4例患者的NKT细胞数量增加，8例患者外周血中检测到自然杀伤活性增强。
发现将α-GalCer脉冲APC注入鼻黏膜下层是安全的，并能在一些患者中诱导抗肿瘤活性。
