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微粒口服乳腺癌疫苗的研制与评价。

Formulation and evaluation of a particulate oral breast cancer vaccine.

机构信息

Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, Georgia 30341, USA.

出版信息

J Pharm Sci. 2012 Oct;101(10):3661-71. doi: 10.1002/jps.23275. Epub 2012 Jul 24.

DOI:10.1002/jps.23275
PMID:22828873
Abstract

Breast cancer being the most fatal form of cancer for female population, justifies exploration of immunotherapy as an alternative treatment. Here, we have formulated and evaluated an oral microparticulate breast cancer vaccine to provide a new line of therapy. The whole cell lysate of 4T07 murine breast cancer cells was incorporated in an aqueous polymer matrix and spray dried to formulate an enteric protected vaccine microparticle. These particles were characterized in vitro and then administered orally to female Balb/c mice in successive boosters. Serum antibody titers during the study were analyzed using enzyme-linked immunosorbent assay. Postvaccination animals were challenged with live 4T07 cells, and tumor growth was monitored. Flow cytometry studies were performed to analyze the role of T cells. Results show that the vaccine microparticles were 1-4 µm in volume diameter and neutral in charge. The particles were protected enterically and had sustained-release profile. Serum antibody titers of vaccinated animals increased significantly after boosters compared with controls (p < 0.05). Tumor challenge studies revealed that vaccinated animals developed significantly smaller tumors (p < 0.05). Significantly higher numbers of CD4(+) cells occurred in vaccinated animals (p < 0.05). Thus, we conclude that the particulate oral breast cancer vaccine was effective in providing protective immune response in the murine model.

摘要

乳腺癌是女性中最致命的癌症形式,因此有理由探索免疫疗法作为一种替代治疗方法。在这里,我们设计并评估了一种口服微粒乳腺癌疫苗,以提供一种新的治疗方法。将 4T07 鼠乳腺癌细胞的全细胞裂解物掺入水性聚合物基质中,并通过喷雾干燥制成肠溶保护疫苗微粒。对这些颗粒进行了体外表征,然后连续加强免疫口服给予雌性 Balb/c 小鼠。在研究过程中使用酶联免疫吸附试验分析血清抗体滴度。接种后的动物用活 4T07 细胞进行攻击,并监测肿瘤生长。进行流式细胞术研究以分析 T 细胞的作用。结果表明,疫苗微粒的体积直径为 1-4 µm,带中性电荷。这些颗粒具有肠溶保护作用,并具有缓释特性。与对照组相比,加强免疫后的疫苗接种动物的血清抗体滴度显著增加(p < 0.05)。肿瘤攻击研究表明,接种疫苗的动物形成的肿瘤明显较小(p < 0.05)。接种疫苗的动物中 CD4(+) 细胞的数量明显更高(p < 0.05)。因此,我们得出结论,微粒口服乳腺癌疫苗在提供保护性免疫应答方面在小鼠模型中是有效的。

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