CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study.
Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
同种异体肿瘤裂解物-DC 治疗可行、安全，并能诱导对 PDAC 表达抗原的免疫反应。
胰腺导管腺癌（PDAC）即使经过根治性切除，其预后也极差。对免疫治疗的反应罕见，这与T细胞启动不足有关。我们此前在临床前模型中证明了同种异体裂解物-树突状细胞（DC）疫苗的效力。在此，我们将这一概念转化应用于患者。
在这项I期研究中，纳入的是接受标准治疗后无影像学复发征象的已切除PDAC患者。在第0、2、4周以及第3和第6个月注射负载同种异体肿瘤裂解物的自体单核细胞来源DC。研究目标是同种异体肿瘤-DC的可行性、安全性和免疫原性。研究了疫苗与患者肿瘤之间共享的肿瘤抗原的存在情况。对外周血、皮肤和肿瘤进行了免疫学分析。
共纳入10例患者。DC制备和给药均成功。所有患者均出现1级注射部位及输注相关反应。2例患者出现2级发热，1例患者出现3级呼吸困难。未观察到疫苗相关严重不良事件。在疫苗与患者肿瘤之间发现了共享肿瘤抗原。所有可评估患者均显示出疫苗诱导的应答，表现为Ki67+和活化PD-1+循环T细胞频率增加。此外，检测到治疗诱导的针对研究患者自体肿瘤的T细胞反应性。在中位随访25个月（15-32个月）时，10例患者中有7例未出现疾病复发或进展。
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients.
In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour.
Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15-32 months).
Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens.
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