利用抗原蛋白靶向 APC 的系统开发有效的癌症疫苗。
Development of effective cancer vaccine using targeting system of antigen protein to APCs.
机构信息
Department of Drug Delivery Research Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
出版信息
Pharm Res. 2012 Feb;29(2):483-9. doi: 10.1007/s11095-011-0571-x. Epub 2011 Sep 2.
PURPOSE
To develop a novel cancer vaccine using the targeting system of antigen protein to antigen-presenting cells (APCs) for efficient and safe cancer therapy.
METHODS
The novel delivery system was constructed with antigen protein, benzalkonium chloride (BK), and γ-polyglutamic acid (γ-PGA), using ovalbumin (OVA) as a model antigen protein and evaluating its immune induction effects and utilities for cancer vaccine.
RESULTS
BK and γ-PGA enabled encapsulation of OVA and formed stable anionic particles at nanoscale, OVA/BK/γ-PGA complex. Complex was taken up by dendritic cell line DC2.4 cells efficiently. We subcutaneously administered the complex to mice and examined induction of IgGs. The complex induced not only Th2-type immunoglobulins but also Th1-type immunoglobulins. OVA/BK/γ-PGA complex inhibited tumor growth of E.G7 cells expressing OVA regularly; administered OVA/BK/γ-PGA complex completely rejected tumor cells.
CONCLUSION
The novel vaccine could be platform technology for a cancer vaccine.
目的
利用抗原蛋白靶向抗原呈递细胞（APCs）的靶向系统，开发一种新型癌症疫苗，以实现高效、安全的癌症治疗。
方法
以卵清蛋白（OVA）为模型抗原蛋白，构建新型递药系统，包括抗原蛋白、苯扎氯铵（BK）和γ-聚谷氨酸（γ-PGA），并评估其免疫诱导效果及其作为癌症疫苗的用途。
结果
BK 和 γ-PGA 可包裹 OVA 并在纳米尺度形成稳定的阴离子颗粒，即 OVA/BK/γ-PGA 复合物。复合物可被树突状细胞系 DC2.4 细胞有效摄取。我们将复合物皮下注射到小鼠体内，并检测 IgG 的诱导情况。复合物不仅诱导了 Th2 型免疫球蛋白，还诱导了 Th1 型免疫球蛋白。OVA/BK/γ-PGA 复合物可抑制常规表达 OVA 的 E.G7 细胞的肿瘤生长；给予 OVA/BK/γ-PGA 复合物可完全排斥肿瘤细胞。
结论
新型疫苗可能成为癌症疫苗的平台技术。
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