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来自一项纳妥单抗依司他托克斯联合干扰素-α与干扰素-α对比的随机2/3期研究中晚期肾细胞癌患者亚组的免疫反应和总生存期

Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α.

作者信息

Elkord Eyad, Burt Deborah J, Sundstedt Anette, Nordle Örjan, Hedlund Gunnar, Hawkins Robert E

机构信息

Department of Medical Oncology, Institute of Cancer Sciences, The University of Manchester, Manchester, UK.

Department of Medical Microbiology & Immunology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE.

出版信息

Oncotarget. 2015 Feb 28;6(6):4428-39. doi: 10.18632/oncotarget.2922.

DOI:10.18632/oncotarget.2922
PMID:25669986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4414201/
Abstract

Naptumomab estafenatox/ABR-217620/ANYARA (Nap) has been evaluated in clinical phase 1 and 2/3 studies. RCC patients in the phase 2/3 trial were randomized 1:1 in an open label study to receive Nap+IFN-α or IFN-α. In this study, we analyzed the UK patients for their immunological response in relation to prolonged overall survival (OS). We found that Nap-specific T cells were reduced after 3 treatment days in patients' peripheral blood. Levels of both Nap-specific CD4+ and CD8+ T cells were significantly higher 8 days after the first treatment. Patients with such pattern of reduction and expansion of Nap-binding T cells also showed increased levels of IL-2 and IFN-γ in plasma 3 hours after the first Nap treatment. In addition, Nap caused an increase of IL-6, IL-10 and TNF-α. The patients in the UK subset showed a tendency of OS benefit after Nap treatment. Most Nap treated patients with long OS had low baseline IL-6 and normal levels of anti-SEA/E-120 antibodies. Furthermore, patients with pronounced Nap induced IL-2 and T cell expansion had long OS. In conclusion, patients with low baseline IL-6 and normal anti-SEA/E-120 may respond well to Nap by T cell activation and expansion paving the way for anti-tumour effects.

摘要

纳普妥单抗/ABR-217620/ANYARA（Nap）已在1期和2/3期临床研究中进行了评估。2/3期试验中的肾细胞癌患者在一项开放标签研究中按1:1随机分组，接受Nap+IFN-α或IFN-α治疗。在本研究中，我们分析了英国患者与延长总生存期（OS）相关的免疫反应。我们发现，治疗3天后患者外周血中Nap特异性T细胞减少。首次治疗8天后，Nap特异性CD4+和CD8+T细胞水平均显著升高。具有这种Nap结合T细胞减少和扩增模式的患者在首次Nap治疗3小时后血浆中IL-2和IFN-γ水平也升高。此外，Nap导致IL-6、IL-10和TNF-α增加。英国亚组的患者在接受Nap治疗后有OS获益的趋势。大多数接受Nap治疗且OS长的患者基线IL-6水平低且抗SEA/E-120抗体水平正常。此外，Nap诱导的IL-2和T细胞扩增明显的患者OS长。总之，基线IL-6水平低且抗SEA/E-120正常的患者可能通过T细胞激活和扩增对Nap反应良好，为抗肿瘤作用铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/9adca9c46496/oncotarget-06-4428-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/03119ad6b0ee/oncotarget-06-4428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/979de4ade8b4/oncotarget-06-4428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/9b177c9fb514/oncotarget-06-4428-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/a4ecbdd99815/oncotarget-06-4428-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/9bb28721fc2e/oncotarget-06-4428-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/9adca9c46496/oncotarget-06-4428-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/03119ad6b0ee/oncotarget-06-4428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/979de4ade8b4/oncotarget-06-4428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/9b177c9fb514/oncotarget-06-4428-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/a4ecbdd99815/oncotarget-06-4428-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/9bb28721fc2e/oncotarget-06-4428-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/4414201/9adca9c46496/oncotarget-06-4428-g006.jpg

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