癌症免疫治疗中的阿尔法病毒。
Alphaviruses in cancer immunotherapy.
发表日期:2023
作者:
Kenneth Lundstrom
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
阿尔法病毒经常被用于癌症治疗、肿瘤免疫疗法和癌症疫苗的开发。作为自复制RNA病毒的成员,阿尔法病毒通过高效的RNA基因组在宿主细胞中自我复制,提供了高水平的转基因表达。阿尔法病毒载体可作为重组病毒颗粒或溶瘤病毒使用。另外,裸RNA和DNA复制子可以利用纳米颗粒来包装。在癌症预防和治疗的背景下,从阿尔法病毒载体中表达抗肿瘤、细胞毒和自杀基因,以实现肿瘤的回归和消除。此外,也可以利用免疫刺激基因如细胞因子和趋化因子来进行癌症免疫疗法的研究。肿瘤抗原的表达也被应用于癌症疫苗的开发。阿尔法病毒载体在多种临床前动物模型中显示出肿瘤的回归和甚至治愈效果。免疫接种引发了强大的免疫应答,并在动物模型中对抗肿瘤细胞具有保护作用。几项临床试验证实了阿尔法病毒在癌症患者中的良好安全性和耐受性,尽管治疗效果仍需要进一步优化。版权所有 © 2023 Elsevier Inc. 保留所有权利。
Alphaviruses have frequently been engineered for cancer therapy, cancer immunotherapy, and cancer vaccine development. As members of self-replicating RNA viruses, alphaviruses provide high levels of transgene expression through efficient self-amplifying of their RNA genome in host cells. Alphavirus vectors can be used as recombinant viral particles or oncolytic viruses. Alternatively, either naked or nanoparticle-encapsulated RNA and DNA replicons can be utilized. In the context of cancer prevention and treatment, antitumor, cytotoxic and suicide genes have been expressed from alphavirus vectors to provide tumor regression and tumor eradication. Moreover, immunostimulatory genes such as cytokines and chemokines have been used for cancer immunotherapy approaches. Expression of tumor antigens has been applied for cancer vaccine development. Alphavirus vectors has demonstrated tumor regression and even cure in various preclinical animal models. Immunization has elicited strong immune responses and showed protection against challenges with tumor cells in animal models. Several clinical trials have confirmed good safety and tolerability of alphaviruses in cancer patients although therapeutic efficacy will still require optimization.Copyright © 2023 Elsevier Inc. All rights reserved.