Shaw Amanda Rosewell, Suzuki Masataka
Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Baylor College of Medicine, Center for Cell Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX, USA.
Mol Ther Methods Clin Dev. 2019 Nov 13;15:418-429. doi: 10.1016/j.omtm.2019.11.001. eCollection 2019 Dec 13.
Adenoviruses are a commonly utilized virus for gene therapy platforms worldwide. Since adenovirus components are characterized as highly immunogenic, their immunogenicity inhibits the widespread use of adenoviral vectors to treat genetic disorders. However, stimulation of the immune response can be exploited for cancer immunotherapy platforms, and thus adenoviral vectors are used for therapeutic gene transfer, vaccines, and oncolytic agents in the cancer gene therapy field. It is now accepted that the generation of anti-tumor immune responses induced by oncolytic adenovirus treatments is critical for their anti-tumor efficacy. As such, in cancer immunotherapy with adenoviral vectors, a balance must be struck between induction of anti-adenoviral and anti-tumor immune responses. The recent trend in adenoviral-based cancer gene therapy is the development of adenoviral vectors to enhance immune responses and redirect them toward tumors. This review focuses on anti-adenoviral immunity and how adenovirotherapies skew the immune response toward an anti-tumor response.
腺病毒是全球基因治疗平台常用的病毒。由于腺病毒成分具有高度免疫原性,其免疫原性抑制了腺病毒载体在治疗遗传疾病方面的广泛应用。然而,免疫反应的刺激可用于癌症免疫治疗平台,因此腺病毒载体在癌症基因治疗领域用于治疗性基因转移、疫苗和溶瘤药物。目前人们认为,溶瘤腺病毒治疗诱导的抗肿瘤免疫反应的产生对其抗肿瘤疗效至关重要。因此,在用腺病毒载体进行癌症免疫治疗时,必须在诱导抗腺病毒和抗肿瘤免疫反应之间取得平衡。基于腺病毒的癌症基因治疗的最新趋势是开发腺病毒载体,以增强免疫反应并使其重新导向肿瘤。本综述重点关注抗腺病毒免疫以及腺病毒疗法如何使免疫反应偏向抗肿瘤反应。