Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, Mercer University, College of Pharmacy and Health Sciences, Atlanta, GA 30341, USA.
Vaccine. 2012 Aug 17;30(38):5675-81. doi: 10.1016/j.vaccine.2012.05.073. Epub 2012 Jun 28.
Ovarian cancer is the fifth most leading cause of cancer related deaths in women in the US. Customized immunotherapeutic strategies may serve as an alternative method to control the recurrence or progression of ovarian cancer and to avoid severe adverse effects of chemotherapy. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared with the use of a spray dryer. These particles were designed for oral delivery using enteric polymers such as methacrylic copolymer, Eudragit(®) FS30D and hydroxyl propyl methyl cellulose acetate succinate. These particles were targeted for uptake via microfold cell (M-cell) in Peyer's patches of small intestine using M-cell targeting ligand, Aleuria aurantia lectin. The interleukins (ILs) such as IL-2 and IL-12 were added to the vaccine formulation to further enhance the immune response. The particles obtained were of 1.58±0.62 μm size with a charge of 12.48±2.32 mV. The vaccine efficacy was evaluated by administering the particles via oral route to C57BL/6 female mice. At the end of vaccination, mice were challenged with live tumor cells. Vaccinated mice showed significant (around six-fold) retardation of tumor volume in comparison to non-vaccinated animals for 3 weeks after the tumor challenge (p<0.001). The serum IgG antibody levels were found to be elevated in case of vaccinated animals in comparison to non-vaccinated group (p<0.05). Analysis of IgG1 titers (indicative of Th2 response) and IgG2a titers (indicative of Th1 response) showed a mixed Th1 and Th2 immune response in case vaccine alone and Th2 response in case of vaccine with interleukins group. Moreover, CD8+ T-cell, CD4+ T-cell and B-cell populations in different lymphatic organs were elevated in case of vaccinated mice. Thus, whole cell lysate vaccine microparticles formulated by spray drying could trigger humoral as well as cellular immune response when administered orally. Such vaccine could potentially be an effective treatment for patients with residual tumor or high tumor-relapse probability.
卵巢癌是美国女性癌症相关死亡的第五大主要原因。定制的免疫治疗策略可能是一种替代方法，可以控制卵巢癌的复发或进展，并避免化疗的严重不良反应。在这项研究中，使用喷雾干燥器制备了一种使用小鼠卵巢癌细胞系 ID8 的全细胞裂解物的微粒疫苗。这些颗粒设计用于通过肠溶聚合物（如甲基丙烯酸共聚物、Eudragit®FS30D 和羟丙基甲基纤维素醋酸琥珀酸酯）进行口服给药。这些颗粒使用甘露糖受体靶向配体，舞茸 Aurantia 凝集素，靶向小肠派尔集合淋巴结中的微褶细胞（M 细胞）摄取。白细胞介素（ILs），如 IL-2 和 IL-12，被添加到疫苗配方中，以进一步增强免疫反应。获得的颗粒粒径为 1.58±0.62μm，带电量为 12.48±2.32mV。通过口服途径向 C57BL/6 雌性小鼠给予颗粒来评估疫苗的功效。在接种结束时，用活肿瘤细胞对小鼠进行攻毒。与未接种疫苗的动物相比，接种疫苗的小鼠在肿瘤攻毒后 3 周内肿瘤体积显著（约 6 倍）延迟（p<0.001）。与未接种疫苗的组相比，接种疫苗的动物的血清 IgG 抗体水平升高（p<0.05）。分析 IgG1 效价（指示 Th2 反应）和 IgG2a 效价（指示 Th1 反应）表明，单独疫苗组表现出混合 Th1 和 Th2 免疫反应，而白细胞介素组则表现出 Th2 反应。此外，接种疫苗的小鼠不同淋巴器官中的 CD8+T 细胞、CD4+T 细胞和 B 细胞群体增加。因此，通过喷雾干燥制备的全细胞裂解物疫苗微粒在口服给药时可以引发体液和细胞免疫反应。这种疫苗可能是治疗残留肿瘤或高肿瘤复发概率患者的有效方法。
