研究动态
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癌症免疫疗法中的装甲改良天花病毒安卡拉。

Armored modified vaccinia Ankara in cancer immunotherapy.

发表日期:2023
作者: Cigdem Atay, José Medina-Echeverz, Hubertus Hochrein, Mark Suter, Maria Hinterberger
来源: International Review of Cell and Molecular Biology

摘要:

癌症免疫疗法依赖于激活患者的免疫系统对肿瘤细胞进行攻击。癌症疫苗的目标是通过刺激先天免疫和适应性免疫来实现持久的临床反应。临床上成功开发癌症疫苗的一些障碍包括肿瘤抗原的选择、用于增强抗肿瘤特异性免疫反应的佐剂以及与增强与免疫相关的不良效应的风险有关的问题。修改后痘苗(MVA)属于痘病毒家族,是一个多功能疫苗平台,结合了癌症治疗所需的几个重要特征。首先,MVA是诱导先天免疫反应的优秀药物,可导致I型干扰素的分泌和T辅助细胞类型1(Th1)免疫反应的诱导。其次,它能引起强大而持久的体液和细胞免疫反应,以对病毒编码的异源抗原进行应答。第三,MVA具有巨大的基因组灵活性,能表达多种抗原和共刺激实体。第四,其在人体细胞中的复制缺陷确保了良好的安全性。本综述总结了MVA如何诱导先天和适应性免疫反应的当前认识。此外,我们介绍了已用于改良MVA并描述其临床应用的肿瘤相关抗原和免疫调节分子的概述。最后,将讨论MVA免疫途径及其对治疗效果的影响,具体取决于表达的免疫调节分子。版权所有© 2023 Elsevier Inc. 发布。
Cancer immunotherapy relies on unleashing the patient´s immune system against tumor cells. Cancer vaccines aim to stimulate both the innate and adaptive arms of immunity to achieve durable clinical responses. Some roadblocks for a successful cancer vaccine in the clinic include the tumor antigen of choice, the adjuvants employed to strengthen antitumor-specific immune responses, and the risks associated with enhancing immune-related adverse effects in patients. Modified vaccinia Ankara (MVA) belongs to the family of poxviruses and is a versatile vaccine platform that combines several attributes crucial for cancer therapy. First, MVA is an excellent inducer of innate immune responses leading to type I interferon secretion and induction of T helper cell type 1 (Th1) immune responses. Second, it elicits robust and durable humoral and cellular immunity against vector-encoded heterologous antigens. Third, MVA has enormous genomic flexibility, which allows for the expression of multiple antigenic and costimulatory entities. And fourth, its replication deficit in human cells ensures a excellent safety profile. In this review, we summarize the current understanding of how MVA induces innate and adaptive immune responses. Furthermore, we will give an overview of the tumor-associated antigens and immunomodulatory molecules that have been used to armor MVA and describe their clinical use. Finally, the route of MVA immunization and its impact on therapeutic efficacy depending on the immunomodulatory molecules expressed will be discussed.Copyright © 2023. Published by Elsevier Inc.