Mork Family Department of Chemical Engineering and Material Science, University of Southern California, Los Angeles, CA 90089, USA.
Hum Gene Ther. 2009 Dec;20(12):1652-64. doi: 10.1089/hum.2009.012.
It has been demonstrated that nonintegrating lentiviral vectors (NILVs) are efficient in maintaining transgene expression in vitro and in vivo. Gene delivery by NILVs can significantly reduce nonspecific vector integration, which has been shown to cause malignant transformation in patients receiving gene therapy for X-linked severe combined immunodeficiency. Strong and sustained immune responses were observed after a single immunization with NILVs carrying viral antigens. However, there is no report to date that evaluates the efficacy of NILVs in inducing antigen-specific antitumor immunity. Using a well-characterized tumor model, we tested in vivo immunization with a self-inactivating lentiviral vector harboring a defective integrase. A high frequency of ovalbumin peptide (OVAp1)-specific CD8(+) T cells and a substantial antibody response were detected in naive mice immunized with an NILV encoding an OVA transgene. Furthermore, this immunization method completely protected the mice against the growth of E.G7 tumor cells expressing the OVA antigen. Thus, this study provides evidence that immunization using NILVs can be a safe and promising approach for exploring cancer immunotherapy.
已证实,非整合慢病毒载体(NILVs)在体外和体内均能有效地维持转基因的表达。NILVs 的基因传递可显著减少非特异性载体整合,这已被证明会导致接受 X 连锁严重联合免疫缺陷症基因治疗的患者发生恶性转化。用携带病毒抗原的 NILV 进行单次免疫接种后,可观察到强烈和持续的免疫应答。然而,目前尚无报道评估 NILVs 在诱导抗原特异性抗肿瘤免疫中的功效。我们使用一种经过良好表征的肿瘤模型,在体内测试了携带缺陷整合酶的自失活慢病毒载体的免疫接种。在接受编码 OVA 转基因的 NILV 免疫接种的幼稚小鼠中,检测到高频率的卵清蛋白肽(OVA p1)特异性 CD8(+)T 细胞和大量抗体应答。此外,这种免疫接种方法可完全防止表达 OVA 抗原的 E.G7 肿瘤细胞的生长。因此,这项研究提供了证据,表明使用 NILVs 进行免疫接种可能是探索癌症免疫疗法的一种安全且有前途的方法。