Phase I study of α-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer
Phase I study of α-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer
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DOI：
10.1007/s00262-007-0373-5
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发表时间：
2008-03-01
影响因子：
5.8
通讯作者：
Okamoto, Yoshitaka
中科院分区：
文献类型：
--
作者：
Uchida, Tetsuro;Horiguchi, Shigetoshi;Okamoto, Yoshitaka
人类V α 24自然杀伤T （NKT）细胞被特异性配体α -半乳糖神经酰胺（α - galcer）以cd1依赖的方式激活。活化的NKT细胞具有很强的抗肿瘤活性。方法采用α - galcer脉冲抗原提呈细胞（APCs）对头颈癌患者鼻黏膜下进行I期研究，评估该治疗方法的安全性和可行性。9例不可切除或复发的头颈癌患者接受两次治疗，间隔1周，1 x(8)次α - galcer脉冲自体APCs进入鼻粘膜下层。结果在临床研究期间，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）。第一次和第二次给予α - galcer脉冲APCs后，4例患者的NKT细胞数量增加，8例患者的外周血中检测到自然杀伤活性增强。结论经α - galcer脉冲APCs鼻粘膜下给药是安全的，在部分患者中具有抗肿瘤活性。
Background Human V alpha 24 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.Methods 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(8) of alpha-GalCer-pulsed autologous APCs into the nasal submucosa.Results 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.Conclusion The administration of alpha-GalCer-pulsed APCs into the nasal submucosa was found to be safe and induce anti-tumor activity in some patients.