Hamdy Samar, Molavi Ommoleila, Ma Zengshuan, Haddadi Azita, Alshamsan Aws, Gobti Zahra, Elhasi Sara, Samuel John, Lavasanifar Afsaneh
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada.
Vaccine. 2008 Sep 15;26(39):5046-57. doi: 10.1016/j.vaccine.2008.07.035. Epub 2008 Aug 3.
The purpose of this study was to evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA)-based vaccines in breaking immunotolerance to cancer-associated self-antigens. Vaccination of mice bearing melanoma B16 tumors with PLGA nanoparticles (NP) co-encapsulating the poorly immunogenic melanoma antigen, tyrosinase-related protein 2 (TRP2), along with Toll-like receptor (TLR) ligand (7-acyl lipid A) was examined. Remarkably, this vaccine was able to induce therapeutic anti-tumor effect. Activated TRP2-specific CD8 T cells were capable of interferon (IFN)-gamma secretion at lymph nodes and spleens of the vaccinated mice. More importantly, TRP2/7-acyl lipid A-NP treated group has shown immunostimulatory milieu at the tumor microenvironment, as evidenced by increased level of pro-inflammatory cytokines compared to control group. These results support the potential use of PLGA nanoparticles as competent carriers for future cancer vaccine formulations.
本研究的目的是评估基于聚乳酸-乙醇酸共聚物（PLGA）的疫苗在打破对癌症相关自身抗原的免疫耐受方面的疗效。研究人员检测了用共包裹免疫原性较差的黑色素瘤抗原酪氨酸酶相关蛋白2（TRP2）和Toll样受体（TLR）配体（7-酰基脂质A）的PLGA纳米颗粒（NP）对携带黑色素瘤B16肿瘤的小鼠进行疫苗接种的效果。值得注意的是，这种疫苗能够诱导治疗性抗肿瘤效应。活化的TRP2特异性CD8 T细胞能够在接种疫苗小鼠的淋巴结和脾脏中分泌干扰素（IFN）-γ。更重要的是，与对照组相比，TRP2/7-酰基脂质A-NP治疗组在肿瘤微环境中表现出免疫刺激环境，促炎细胞因子水平升高证明了这一点。这些结果支持了PLGA纳米颗粒作为未来癌症疫苗制剂的有效载体的潜在用途。
