Samford University, McWhorter School of Pharmacy, Birmingham, AL, USA.
J Drug Target. 2012 Feb;20(2):166-73. doi: 10.3109/1061186X.2011.622395. Epub 2011 Oct 10.
Cancer vaccines are limited in their use, because of their inability to mount a robust anti-tumor immune response. Thus, targeting M-cells in the small intestine, which are responsible for entry of many pathogens, will be an attractive way to elicit a strong immune response toward particulate antigens. Therefore, in the present investigation, we demonstrated that efficient oral vaccination against melanoma antigens could be accomplished by incorporating the antigens in an albumin-based microparticle with a ligand AAL (Aleuria aurantia lectin) targeted specifically to M-cells. The oral microparticulate vaccine effectively protected the mice from subcutaneous challenge with tumor cells in prophylactic settings. The animals were vaccinated with antigen microparticles having a size range of around 1-1.25 µm where one prime and four booster doses were administered every 14 days over 10 weeks of duration, followed by challenge with live tumor cells, which showed complete tumor protection after oral vaccination. With the inclusion of ligand in the microparticles, we observed significantly higher IgG titers (1565 μg/mL) as compared to the microparticle formulations without AAL (872 μg/mL). This data suggests that ligand loaded microparticles may have the potential to target antigens to M-cells for an efficient oral vaccination.
癌症疫苗的应用受到限制，因为它们无法引发强大的抗肿瘤免疫反应。因此，针对小肠中的 M 细胞（负责许多病原体进入的细胞）将是一种有吸引力的方法，可以引发针对颗粒性抗原的强烈免疫反应。因此，在本研究中，我们证明了通过将抗原结合到一种基于白蛋白的微颗粒中，并使用专门针对 M 细胞的配体 AAL（Aleuria aurantia lectin），可以有效地实现针对黑色素瘤抗原的高效口服疫苗接种。口服微粒疫苗在预防性设置中有效地保护了小鼠免受皮下肿瘤细胞的挑战。在 10 周的时间内，每隔 14 天给予一次抗原微颗粒的一次初免和四次加强免疫，随后用活肿瘤细胞进行挑战，口服疫苗接种后完全保护了肿瘤。在微颗粒中加入配体后，我们观察到与没有 AAL 的微颗粒制剂（872μg/mL）相比，IgG 滴度（1565μg/mL）显著升高。该数据表明，负载配体的微粒可能具有将抗原靶向 M 细胞以进行有效口服疫苗接种的潜力。
