Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
Finnish Centre for Laboratory Animal Pathology and Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki , Helsinki, Finland.
Mol Ther Oncolytics. 2014 Dec 10;1:14002. doi: 10.1038/mto.2014.2. eCollection 2014.
We evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding CD40 ligand in two Beagles, in preparation for a phase 1 trial in canine cancer patients. Dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. Dogs were monitored for adverse events and underwent a detailed postmortem examination. Blood, saliva, urine, feces, and organs were collected for virus detection. Dog 1 had mild fever and lethargy while dog 2 experienced a possible seizure 5.5 hours after first virus administration. Viral DNA declined quickly in the blood after virus administration in both dogs but was still detectable 1 week later by quantitative polymerase chain reaction. Only samples taken directly after virus infusion contained infectious virus. Small amounts of viral DNA, but no infectious virus, were detected in a few saliva and urine samples. Necropsies did not reveal any relevant pathological changes and virus DNA was detected mainly in the spleen. The dogs in the study did not have cancer, and thus adverse events could be more common and viral load higher in dogs with tumors which allow viral amplification.
我们评估了在两只比格犬中表达 CD40 配体的溶瘤痘苗病毒的不良事件、生物分布和脱落情况，为犬科癌症患者的 I 期临床试验做准备。狗 1 接受了一剂痘苗病毒，24 小时后安乐死，而狗 2 每周接受一次病毒治疗，共四次，然后在 7 天后安乐死。对狗进行了不良事件监测，并进行了详细的尸检。采集血液、唾液、尿液、粪便和器官进行病毒检测。狗 1 有轻度发热和嗜睡，而狗 2 在第一次病毒给药后 5.5 小时出现可能的癫痫发作。在两只狗中，病毒给药后血液中的病毒 DNA 迅速下降，但通过定量聚合酶链反应仍可在 1 周后检测到。只有在病毒输注后直接采集的样本才含有感染性病毒。少数唾液和尿液样本中检测到少量的病毒 DNA，但没有检测到感染性病毒。尸检未发现任何相关的病理变化，病毒 DNA 主要在脾脏中检测到。研究中的狗没有癌症，因此在允许病毒扩增的肿瘤犬中，不良事件可能更常见，病毒载量也更高。
