Whiteside Theresa L, Ferris Robert L, Szczepanski Miroslaw, Tublin Mitchell, Kiss Joseph, Johnson Rita, Johnson Jonas T
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Head Neck. 2016 Apr;38 Suppl 1(Suppl 1):E494-501. doi: 10.1002/hed.24025. Epub 2015 Jul 15.
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.
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.
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.
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.
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。
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。
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。
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。