Pan Therapeutics, Lutry, Switzerland.
Int Rev Cell Mol Biol. 2023;379:143-168. doi: 10.1016/bs.ircmb.2023.03.011. Epub 2023 Jun 14.
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.
甲病毒已被广泛用于癌症治疗、癌症免疫疗法和癌症疫苗的开发。作为自我复制的 RNA 病毒的成员，甲病毒通过在宿主细胞中高效地自我扩增其 RNA 基因组，提供高水平的转基因表达。甲病毒载体可用作重组病毒颗粒或溶瘤病毒。或者，可以使用裸露的或纳米颗粒包封的 RNA 和 DNA 复制子。在癌症预防和治疗方面，已经从甲病毒载体表达抗肿瘤、细胞毒性和自杀基因，以提供肿瘤消退和肿瘤根除。此外，还使用细胞因子和趋化因子等免疫刺激基因进行癌症免疫治疗方法。肿瘤抗原的表达已用于癌症疫苗的开发。甲病毒载体已在各种临床前动物模型中显示出肿瘤消退甚至治愈的效果。免疫接种在动物模型中引发了强烈的免疫反应，并显示出对肿瘤细胞挑战的保护作用。尽管治疗效果仍需优化，但一些临床试验已证实了癌症患者中甲病毒的良好安全性和耐受性。
