a Center of Molecular Immunology (CIM); Immunobiology Division; Atabey; Havana Cuba.
Hum Vaccin Immunother. 2014;10(8):2312-20. doi: 10.4161/hv.29161.
While the NGcGM3/VSSP vaccine, a preparation consisting in very small sized proteoliposomes (VSSP) obtained by the incorporation of the NGcGM3 ganglioside into the outer membrane protein (OMP) complex of Neisseria meningitides, is currently studied in late stage clinical trials in breast cancer and melanoma patients, mechanisms involved in the vaccine's antitumor effect are insufficiently understood. Here we have addressed the role of adaptive and innate immune cells in mediating the protective effect of the vaccine. To this aim we selected the 3LL-D122 Lewis lung spontaneous metastasis model. Unexpectedly, inoculation of the vaccine in tumor bearing C57BL/6 mice, either by subcutaneous (sc) or intraperitoneal (ip) routes, induced similar anti-metastatic effect. Regardless the T-independent nature of NGcGM3 ganglioside as antigen, the antimetastatic effect of NGcGM3/VSSP is dependent on CD4(+) T cells. In a further step we found that the vaccine was able to promote the increase, maturation, and cytokine secretion of conventional DCs and the maturation of Bone Marrow-derived plasmacytoid DCs. In line with this result the in vivo IFNα serum level in ip vaccinated mice increased as soon as 2h after treatment. On the other hand the infiltration of NK1.1(+)CD3(-) and NK1.1(+)CD3(+) cells in lungs of vaccinated mice was significantly increased, compared with the presence of these cells in control animal lungs. In the same way NGcGM3/VSSP mobilized acquired immunity effector cells into the lungs of vaccinated tumor bearing mice. Finally and not less noteworthy, leukocyte infiltration in lungs of tumor bearing mice correlates with vaccine induced inhibition of lung metastization.
尽管 NGcGM3/VSSP 疫苗目前正在乳腺癌和黑色素瘤患者的晚期临床试验中进行研究，该疫苗是由神经节苷脂 NGcGM3 掺入脑膜炎奈瑟氏球菌的外膜蛋白（OMP）复合物制成的非常小的脂质体（VSSP）组成的，但疫苗的抗肿瘤作用机制尚不清楚。在这里，我们研究了适应性和先天免疫细胞在介导疫苗的保护作用中的作用。为此，我们选择了 3LL-D122 Lewis 肺自发转移模型。出乎意料的是，无论是通过皮下（sc）还是腹腔内（ip）途径接种疫苗，均可在荷瘤 C57BL/6 小鼠中诱导类似的抗转移作用。尽管 NGcGM3 神经节苷脂作为抗原具有 T 细胞非依赖性，但 NGcGM3/VSSP 的抗转移作用依赖于 CD4(+)T 细胞。在进一步的步骤中，我们发现疫苗能够促进常规 DC 的增加、成熟和细胞因子分泌以及骨髓来源的浆细胞样 DC 的成熟。与这一结果一致的是，ip 接种疫苗的小鼠的 IFNα 血清水平在治疗后 2 小时内就增加了。另一方面，与对照组动物肺部相比，接种疫苗的小鼠肺部 NK1.1(+)CD3(-)和 NK1.1(+)CD3(+)细胞的浸润明显增加。同样，NGcGM3/VSSP 将获得性免疫效应细胞动员到接种疫苗的荷瘤小鼠肺部。最后，同样值得注意的是，肺部白细胞浸润与疫苗诱导的肺转移抑制相关。
