McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, L8S 4L8, Canada.
CANSWERS, Clinical Trial Division, Georgetown, Ontario, L7G 5L8, Canada.
Sci Rep. 2017 Nov 16;7(1):15738. doi: 10.1038/s41598-017-15992-4.
Direct killing of malignant cells combined with induction of tumour-specific immune responses makes oncolytic vaccines attractive for cancer therapy. We previously developed a heterologous cancer immunization strategy that utilized a replication-defective adenovirus-vectored primary vaccine encoding a tumour antigen followed by boosting with a replication-competent Maraba virus expressing the same antigen. To assess the safety of oncolytic Maraba virus-based booster vaccines and inform the design of clinical trials, we conducted translational studies in cats, which have immune systems that are similar to people and spontaneously develop cancers of comparable types and etiologies. A dose of Maraba virus up to 2.5 × 10 pfu per cat was well-tolerated, with adverse effects limited to mild, transient pyrexia, weight loss, neutropenia, lymphopenia and thrombocytopenia. Maraba viral genomes were present in some urine, stool and most plasma samples up to one week post-infection, but no infectious viruses were recovered. Post-mortem analysis showed one heart, one lung and all spleen samples contained Maraba virus genomes. No replication-competent viruses were recovered from any tissues. Post-mortem histopathological analyses revealed hyperplasia of lymphoid tissues, but no abnormal lesions were attributed to vaccination. This study demonstrated that Maraba virus-vectored cancer vaccines were well-tolerated and supports their use in treating cats.
直接杀伤恶性细胞并诱导肿瘤特异性免疫反应，使溶瘤疫苗成为癌症治疗的一种有吸引力的方法。我们之前开发了一种异源癌症免疫策略，该策略利用复制缺陷型腺病毒载体的初级疫苗编码肿瘤抗原，然后用表达相同抗原的复制型 Maraba 病毒进行加强。为了评估溶瘤 Maraba 病毒增强疫苗的安全性并为临床试验设计提供信息，我们在具有与人相似的免疫系统并自发发展出类似类型和病因的癌症的猫中进行了转化研究。每只猫高达 2.5×10 的 pfu 的 Maraba 病毒剂量耐受性良好，不良反应仅限于轻度、短暂的发热、体重减轻、中性粒细胞减少、淋巴细胞减少和血小板减少。Maraba 病毒基因组存在于一些尿液、粪便和大多数血浆样本中，直到感染后一周，但未回收感染性病毒。尸检分析显示，一颗心脏、一个肺和所有脾脏样本均含有 Maraba 病毒基因组。未从任何组织中回收复制型病毒。尸检组织病理学分析显示淋巴组织增生，但没有异常病变归因于接种。这项研究表明，Maraba 病毒载体癌症疫苗具有良好的耐受性，并支持将其用于治疗猫。
