Randomized phase II trial of a first-in-human cancer cell lysate vaccine in patients with thoracic malignancies.
Randomized phase II trial of a first-in-human cancer cell lysate vaccine in patients with thoracic malignancies.
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DOI：
10.21037/tlcr-21-1
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发表时间：
2021-07
影响因子：
4
通讯作者：
Schrump DS
中科院分区：
文献类型：
--
作者：
Zhang M;Hong JA;Kunst TF;Bond CD;Kenney CM;Warga CL;Yeray J;Lee MJ;Yuno A;Lee S;Miettinen M;Ripley RT;Hoang CD;Gnjatic S;Trepel JB;Schrump DS
虽然大多数恶性肿瘤表达癌睾丸抗原（CTA），这些蛋白质的免疫反应是有限的胸部肿瘤患者。进行该试验以检查癌细胞裂解物疫苗是否可以诱导对CTA的免疫，并确定节拍环磷酰胺和塞来昔布是否增强疫苗诱导的免疫应答。11例原发性胸部恶性肿瘤患者和10例经常规治疗导致NED的胸外肿瘤转移至胸部的患者随机接受H1299肺癌细胞裂解物（10 mg蛋白质/疫苗）和Iscomatrix™佐剂，经皮内深层注射，每4周×6次，每日口服或不口服节拍环磷酰胺/塞来昔布。主要终点是在第6次接种后1个月评估的对纯化CTA的血清学应答。次要终点包括评估环磷酰胺和塞来昔布对疫苗诱导的CTA免疫应答的频率和幅度的影响。探索性终点包括评价疫苗方案对外周免疫亚群的影响。在基线和第3次和第6次疫苗接种后1个月获得标准护理成像研究。所有患者在接种疫苗后均表现出持续72-96小时的局部和全身炎症反应。没有剂量限制性治疗相关毒性。14名患者（67%）完成了所有6次疫苗接种。14例患者中有8例（57%）表现出对NY-ESO-1的血清学应答。一名患者产生了GAGE 7抗体;几名患者表现出对XAGE和MAGE-C2的反应性。疫苗治疗降低了T细胞百分比（P=0.0068）、T细胞上的PD-1表达（P=0.0027）、CD 14+单核细胞上的PD-L1表达（P=0.0089）、经典单核细胞上的PD-L1表达（P=0.016）和中间单核细胞上的PD-L1表达（P=0.0031）。环磷酰胺/塞来昔布似乎没有增加免疫应答或增强疫苗诱导的外周免疫亚群改变。具有Iscomatrix™的H1299裂解物疫苗诱导对CTA的免疫应答，并以可增强胸部恶性肿瘤患者的抗肿瘤免疫的方式调节外周免疫亚群。
Although most malignancies express cancer-testis antigens (CTA), immune responses to these proteins are limited in thoracic oncology patients. This trial was undertaken to examine if a cancer cell lysate vaccine could induce immunity to CTA, and to ascertain if metronomic cyclophosphamide and celecoxib enhances vaccine-induced immune responses. Eleven patients with primary thoracic malignancies and 10 patients with extrathoracic neoplasms metastatic to the chest rendered NED by conventional therapies were randomized to receive H1299 lung cancer cell lysates (10 mg protein/vaccine) with Iscomatrix™ adjuvant via deep intradermal injection q 4 weeks ×6 with or without daily oral metronomic cyclophosphamide/celecoxib. The primary endpoint was serologic response to purified CTA assessed 1 month after the 6th vaccination. Secondary endpoints included assessment of the effects of cyclophosphamide and celecoxib on frequency and magnitude of vaccine-induced immune responses to CTA. Exploratory endpoints included evaluation of the effects of the vaccine regimens on peripheral immune subsets. Standard of care imaging studies were obtained at baseline and 1 month after the 3rd and 6th vaccinations. All patients exhibited local and systemic inflammatory responses lasting 72–96 hours following vaccinations. There were no dose limiting treatment related toxicities. Fourteen patients (67%) completed all six vaccinations. Eight of 14 patients (57%) exhibited serologic responses to NY-ESO-1. One patient developed antibodies to GAGE7; several patients exhibited reactivity to XAGE and MAGE-C2. Vaccine therapy decreased the percent of Tregs (P=0.0068), PD-1 expression on Tregs (P=0.0027), PD-L1 expression on CD14+ monocytes (P=0.0089), PD-L1 expression on classical monocytes (P=0.016), and PD-L1 expression on intermediate monocytes (P=0.0031). Cyclophosphamide/celecoxib did not appear to increase immune responses or enhance vaccine-induced alterations in peripheral immune subsets. H1299 lysate vaccines with Iscomatrix™ induce immune responses to CTA and modulate peripheral immune subsets in a manner that may enhance antitumor immunity in patients with thoracic malignancies.
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影响因子：
3.3
作者：
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影响因子：
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通讯作者：
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