Yoshikawa Tomoaki, Okada Naoki, Oda Atsushi, Matsuo Keisuke, Matsuo Kazuhiko, Kayamuro Hiroyuki, Ishii Yumiko, Yoshinaga Tomoyo, Akagi Takami, Akashi Mitsuru, Nakagawa Shinsaku
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Vaccine. 2008 Mar 4;26(10):1303-13. doi: 10.1016/j.vaccine.2007.12.037. Epub 2008 Jan 15.
Nanotechnology is a fundamental technology for designing and generating innovative carriers for biomacromolecular drugs. Biodegradable poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent vaccine carriers capable of delivering antigenic proteins to antigen-presenting cells (APCs) and eliciting potent immune responses based on antigen-specific cytotoxic T lymphocytes. In mice, subcutaneous immunization with gamma-PGA NPs entrapping ovalbumin (OVA) more effectively inhibited the growth of OVA-transfected tumors than immunization with OVA emulsified using Freund's complete adjuvant. In addition, gamma-PGA NPs did not induce histopathologic changes after subcutaneous injection or acute toxicity through intravenous injection. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins into APCs, and these antigen-capturing APCs migrated to regional lymph nodes. Our results demonstrate that a gamma-PGA NP system for antigen delivery will advance the clinical utility of vaccines against cancer.
纳米技术是设计和生成用于生物大分子药物的创新载体的一项基础技术。基于可生物降解的聚(γ-谷氨酸)的纳米颗粒(γ-PGA NPs)是出色的疫苗载体,能够将抗原性蛋白递送至抗原呈递细胞(APC),并基于抗原特异性细胞毒性T淋巴细胞引发强烈的免疫反应。在小鼠中,用包裹卵清蛋白(OVA)的γ-PGA NPs进行皮下免疫,比用弗氏完全佐剂乳化的OVA免疫更有效地抑制了OVA转染肿瘤的生长。此外,γ-PGA NPs皮下注射后未诱导组织病理学变化,静脉注射也未引起急性毒性。重要的是,γ-PGA NPs能有效地将包裹的抗原性蛋白递送至APC,并且这些捕获抗原的APC迁移至局部淋巴结。我们的结果表明,用于抗原递送的γ-PGA NP系统将推动抗癌疫苗的临床应用。