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用于头颈部鳞状细胞癌的基于树突状细胞的自体肿瘤疫苗。

Dendritic cell-based autologous tumor vaccines for head and neck squamous cell carcinoma.

作者信息

Whiteside Theresa L, Ferris Robert L, Szczepanski Miroslaw, Tublin Mitchell, Kiss Joseph, Johnson Rita, Johnson Jonas T

机构信息

Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

出版信息

Head Neck. 2016 Apr;38 Suppl 1(Suppl 1):E494-501. doi: 10.1002/hed.24025. Epub 2015 Jul 15.

Abstract

BACKGROUND

An autologous vaccine of apoptotic tumor cells (ATCs) and dendritic cells (DCs) was administered to patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) to study safety and feasibility.

METHODS

Autologous DCs were generated from monocytes, loaded with ATCs, and delivered intranodally. Delayed-type hypersensitivity (DTH) and immunological endpoints were measured prevaccination and postvaccination. Clinical follow-up was required.

RESULTS

Tumors obtained from 30 patients yielded 2 × 10(6) to 2 × 10(8) tumor cells. Only 19 of 30 (63%) were sterile. Ten of 30 patients (33%) had ≥1 × 10(7) sterile tumor cells required for vaccine production. Eight of 10 patients had positive recall DTH. Five of 10 patients were leukapheresed to generate DCs. Four of 5 patients were vaccinated. ATC-reactive T cells were detected in 3 of 4 patients. All 4 patients survived >5 years. The trial failed to enroll the projected 12 patients and was terminated.

CONCLUSION

This vaccine was safe and immunogenic but feasible only in patients with HNSCC with positive prevaccine DTH and ≥1 × 10(7) sterile tumor cells. All vaccinated patients were long-term disease-free survivors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E494-E501, 2016.

摘要

背景

对III/IV期头颈部鳞状细胞癌(HNSCC)患者接种凋亡肿瘤细胞(ATC)和树突状细胞(DC)的自体疫苗,以研究其安全性和可行性。

方法

从单核细胞中生成自体DC,用ATC负载,然后进行结内注射。在接种疫苗前和接种后测量迟发型超敏反应(DTH)和免疫终点指标。需要进行临床随访。

结果

从30例患者获取的肿瘤产生了2×10⁶至2×10⁸个肿瘤细胞。30例中只有19例(63%)无菌。30例患者中有10例(33%)有≥1×10⁷个用于疫苗生产所需的无菌肿瘤细胞。10例患者中有8例回忆性DTH呈阳性。10例患者中有5例进行了白细胞分离术以生成DC。5例患者中有4例接种了疫苗。4例患者中有3例检测到ATC反应性T细胞。所有4例患者存活超过5年。该试验未能招募到预计的12例患者,因此终止。

结论

这种疫苗是安全且具有免疫原性的,但仅对疫苗接种前DTH呈阳性且有≥1×10⁷个无菌肿瘤细胞的HNSCC患者可行。所有接种疫苗的患者均为长期无病生存者。©2015威利期刊公司。《头颈》38:E494 - E501,2016年。

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