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肿瘤造影显示影响接受腺病毒溶瘤免疫疗法治疗的癌症患者长期生存的因素。

Oncograms Visualize Factors Influencing Long-Term Survival of Cancer Patients Treated with Adenoviral Oncolytic Immunotherapy.

作者信息

Hemminki Otto, Oksanen Minna, Taipale Kristian, Liikanen Ilkka, Koski Anniina, Joensuu Timo, Kanerva Anna, Hemminki Akseli

机构信息

Cancer Gene Therapy Group, Department of Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Department of Urology, Helsinki University Hospital, Helsinki, Finland.

出版信息

Mol Ther Oncolytics. 2018 Apr 22;9:41-50. doi: 10.1016/j.omto.2018.04.003. eCollection 2018 Jun 29.

Abstract

The first US Food and Drug Administration (FDA)- and EMA-approved oncolytic virus has been available since 2015. However, there are no markers available that would predict benefit for the individual patient. During 2007-2012, we treated 290 patients with advanced chemotherapy-refractory cancers, using 10 different oncolytic adenoviruses. Treatments were given in a Finnish Medicines Agency (FIMEA)-regulated individualized patient treatment program (the Advanced Therapy Access Program [ATAP]), which required long-term follow-up of patients, which is presented here. Focusing on the longest surviving patients, some key clinical and biological features are presented as "oncograms." Some key attributes that could be captured in the oncogram are suggested to predict treatment response and survival after oncolytic adenovirus treatment. The oncogram includes immunological laboratory parameters assessed in peripheral blood (leukocytes, neutrophil-to-lymphocyte ratio, interleukin-8 [IL-8], HMGB1, anti-viral neutralizing antibody status), features of the patient (gender, performance status), tumor features (histological tumor type, tumor load, region of metastases), and oncolytic virus-specific features (arming of the virus). The retrospective approach used here facilitates verification in a prospective controlled trial setting. To our knowledge, the oncogram is the first holistic attempt to identify the patients most likely to benefit from adenoviral oncolytic virotherapy.

摘要

自2015年起,首款获得美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)批准的溶瘤病毒已可供使用。然而,目前尚无能够预测个体患者是否能从中获益的标志物。在2007年至2012年期间,我们使用10种不同的溶瘤腺病毒对290例晚期化疗难治性癌症患者进行了治疗。治疗是在芬兰药品管理局(FIMEA)监管的个体化患者治疗项目(高级治疗准入项目[ATAP])中进行的,该项目要求对患者进行长期随访,本文将对此进行介绍。聚焦于存活时间最长的患者,一些关键的临床和生物学特征以“肿瘤图谱”的形式呈现。肿瘤图谱中可捕捉到的一些关键属性被认为可预测溶瘤腺病毒治疗后的治疗反应和生存情况。肿瘤图谱包括在外周血中评估的免疫学实验室参数(白细胞、中性粒细胞与淋巴细胞比值、白细胞介素-8[IL-8]、高迁移率族蛋白B1[HMGB1]、抗病毒中和抗体状态)、患者特征(性别、体能状态)、肿瘤特征(组织学肿瘤类型、肿瘤负荷、转移部位)以及溶瘤病毒特异性特征(病毒的武装)。本文采用的回顾性方法便于在前瞻性对照试验环境中进行验证。据我们所知,肿瘤图谱是首次全面尝试识别最有可能从腺病毒溶瘤病毒疗法中获益的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d02/6035494/0928edcfe7eb/gr1.jpg

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