Dietz Laura, Engeland Christine E
Faculty of Biosciences, Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, Heidelberg, Germany.
Research Group Mechanisms of Oncolytic Immunotherapy, Clinical Cooperation Unit Virotherapy, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), University Hospital Heidelberg, Heidelberg, Germany.
Methods Mol Biol. 2020;2058:111-126. doi: 10.1007/978-1-4939-9794-7_7.
With the recognition of oncolytic virotherapy as an immunotherapy, the distinct interactions between oncolytic agents and the immune system have come into focus. The role of the immune system in oncolytic virotherapy is somewhat ambiguous: While preexisting or arising immunity directed against viral antigens may preclude efficient viral replication and spread, immunity directed against tumor antigens is considered essential for long-term treatment success. Aside from the antiviral and antitumor immune status of the patient, the specific immunological microenvironment in a given tumor adds an additional layer of complexity.In this review we focus on the case of measles virus, which has long been known for its multifaceted interplay with the immune system. The high prevalence of measles-neutralizing antibodies in the general population may pose additional challenges. The oncolytic measles virus vector platform offers manifold opportunities for tumor-targeted immunomodulation. This review provides a survey of immunomodulation in the context of measles virotherapy including strategies to suppress or circumvent antiviral immunity as well as enhance antitumor immunity that have been pursued in preclinical and clinical studies. Understanding and selective manipulation of the intricate balance between antiviral and antitumor immunity will be crucial to develop the full potential of oncolytic virotherapy.
随着溶瘤病毒疗法被视为一种免疫疗法，溶瘤剂与免疫系统之间独特的相互作用已成为焦点。免疫系统在溶瘤病毒疗法中的作用有些模糊：虽然针对病毒抗原的预先存在或新出现的免疫可能会妨碍病毒的有效复制和传播，但针对肿瘤抗原的免疫被认为是长期治疗成功的关键。除了患者的抗病毒和抗肿瘤免疫状态外，特定肿瘤中的特定免疫微环境又增加了一层复杂性。在本综述中，我们聚焦于麻疹病毒的情况，长期以来它因其与免疫系统的多方面相互作用而闻名。普通人群中麻疹中和抗体的高流行率可能带来额外挑战。溶瘤麻疹病毒载体平台为肿瘤靶向免疫调节提供了多种机会。本综述概述了麻疹病毒疗法背景下的免疫调节，包括在临床前和临床研究中所采用的抑制或规避抗病毒免疫以及增强抗肿瘤免疫的策略。理解并选择性地调控抗病毒和抗肿瘤免疫之间的复杂平衡，对于充分发挥溶瘤病毒疗法的潜力至关重要。
