离子导入聚合物复合物疫苗对黑色素瘤退化的作用。
The Effect of Iontophoretic-Delivered Polyplex Vaccine on Melanoma Regression.
发表日期:2023
作者:
Rabab A Husseini, Tatsuya Fukuta, Mizune Ozono, Azza A Hasan, Nagia A El Megrab, Kentaro Kogure
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
尽管癌症疫苗的策略是提供对已建立的肿瘤的治疗效果,但迫切需要开发针对非病毒性癌症的预防性疫苗。在本研究中,我们通过阳离子修饰的肿瘤相关抗原(即人源性黑色素瘤gp10025-33肽(KVPRNQDWL-RRRR))和阴离子胞嘧啶-磷酸-鸟苷脱氧核苷酸(CpG-ODN)佐剂之间静电相互作用制备了聚合物复合纳米粒子。我们之前已经通过弱电离子导入(IP)成功地传递了各种亲水性大分子。在此,我们研究了IP在预防性复合物疫苗经皮传递中的有效性。IP成功地在皮肤中建立了疫苗的均匀分布。疫苗的功效已经证明可以抑制黑色素瘤的生长。观察到明显的肿瘤回归效应,以及各种细胞因子(主要为干扰素(IFN)-γ)的mRNA表达水平升高,以及细胞毒性CD8+ T细胞的浸润。此外,我们评估了疫苗的治疗效果,并发现肿瘤负担显著降低。通过上调IFN-γ证实了全身免疫力的刺激作用。这是第一个证明IP在经皮传递预防性黑色素瘤疫苗中使用的报告。
Although the strategy in cancer vaccination is to provide a therapeutic effect against an established tumor, there is an urgent need to develop prophylactic vaccines for non-viral cancers. In this study, we prepared polyplex nanoparticles through electrostatic interactions between a positively-charged modified tumor associated antigen, namely human derived melanoma gp10025-33 peptide (KVPRNQDWL-RRRR), and a negatively charged cytosine-phosphate-guanosine motif (CpG-ODN) adjuvant. We previously demonstrated successful transdermal delivery of various hydrophilic macromolecules by iontophoresis (IP) using weak electricity. Herein, we investigated the effectiveness of IP in the transdermal delivery of a prophylactic polyplex vaccine. IP was successful in establishing a homogenous distribution of the vaccine throughout skin. Efficacy of the vaccine was demonstrated against melanoma growth. A significant tumor regression effect was observed, which was confirmed by elevated mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8+ T cells. Additionally, we evaluated the therapeutic effect of the vaccine and we found a significant reduction in tumor burden. Stimulation of systemic immunity was confirmed by upregulation of IFN-γ. This is the first report to demonstrate the use of IP in the transdermal delivery of a prophylactic melanoma vaccine.