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NKT 细胞靶向过继免疫治疗后肿瘤组织中 NKT 细胞特异性免疫应答的诱导。

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

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

出版信息

Clin Immunol. 2011 Mar;138(3):255-65. doi: 10.1016/j.clim.2010.11.014. Epub 2010 Dec 24.

DOI:10.1016/j.clim.2010.11.014
PMID:21185787
Abstract

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.

摘要

Vα24 自然杀伤 T(NKT)细胞具有强大的抗肿瘤活性。我们使用体外扩增的 Vα24 NKT 细胞和 α-半乳糖神经酰胺(αGalCer;KRN7000)-脉冲抗原呈递细胞(APCs),在局部复发性和可手术治疗的头颈部鳞状细胞癌(HNSCC)患者中进行了一项 II 期临床研究,以研究其疗效和诱导 NKT 细胞特异性免疫应答的能力。受试者为 10 例局部复发和可手术治疗的 HNSCC 患者。在挽救性手术前,通过肿瘤供养动脉给予鼻腔黏膜下单次给予 αGalCer 脉冲 APCs 和经动脉输注激活的 NKT 细胞。评估抗肿瘤作用、切除的癌组织和外周血中的 NKT 细胞特异性免疫应答、安全性和病理作用。5 例患者达到了客观的肿瘤消退。7 例患者的癌组织中 NKT 细胞数量增加,并与肿瘤消退相关。联合治疗在癌组织中诱导了 NKT 细胞特异性免疫应答,与有益的临床效果相关。

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