Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Immunovirotherapy Group, University of Helsinki , Helsinki, Finland.
Mol Ther Oncolytics. 2015 Jan 7;1:14006. doi: 10.1038/mto.2014.6. eCollection 2015.
Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.
成功的癌症控制依赖于克服细胞死亡的抵抗和激活宿主抗肿瘤免疫。溶瘤病毒在这方面特别有吸引力，因为它们可以裂解受感染的肿瘤细胞，并在感染过程中引发强烈的免疫反应。然而，同种病毒的重复注射会促进抗病毒而不是抗肿瘤免疫，并且肿瘤可能会产生先天抗病毒防御来限制溶瘤病毒的复制。在本文中，我们探讨了是否可以通过交替治疗病毒来规避这些问题。我们在两个病毒抗性动物模型中证明，通过交替注射两种免疫上不同的溶瘤病毒，腺病毒和痘苗病毒，可以显著延迟抗病毒免疫和先天细胞反应的诱导。我们的结果支持临床开发异源腺病毒/痘苗病毒治疗癌症。
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