Dendritic cell vaccine for the effective immunotherapy of breast cancer
Dendritic cell vaccine for the effective immunotherapy of breast cancer
复制标题
树突状细胞疫苗用于乳腺癌的有效免疫治疗
DOI：
10.1016/j.biopha.2020.110046
复制
发表时间：
2020-06-01
影响因子：
7.5
通讯作者：
Zhao, Yiqing
中科院分区：
文献类型：
--
作者：
Ni, Jiang;Song, Jinfang;Zhao, Yiqing
癌症疫苗被广泛认为是免疫治疗的有力工具。特别是树突状细胞（DC）有效的抗原加工和提呈特性使其成为开发治疗性肿瘤疫苗的一个有希望的靶点。在我们的研究中，开发了一种通用的癌细胞膜（CCM）涂层碳酸钙（CC）纳米颗粒（MC），能够原位产生肿瘤相关抗原（TAA）用于DC疫苗接种。将小剂量的阿霉素（Dox）包埋在MC的CC核中，可引发免疫原性细胞死亡（ICD）;将光敏剂二氢卟酚e6（Ce 6）包埋在MC的CCM中，通过产生活性氧（ROS），实现有效的光动力学治疗（PDT），最终构建疫苗（MC/Dox/Ce 6）。最重要的是，我们的深入研究揭示了MC/Dox/Ce 6的治疗能够引起TAA群体和DC募集，触发以下免疫应答级联。特别地，可以原位刺激募集的DC细胞用于有效的疫苗接种。体外和体内实验都表明，这种一体化DDS能够增强DC成熟，最终导致在单次施用低剂量Dox和Ce 6时有效抑制乳腺癌的原发性和远处生长。
Cancer vaccine is widely considered as a powerful tool in immunotherapy. In particular, the effective antigen processing and presentation natures of dendritic cell (DC) have made it a promising target for the development of therapeutic vaccine for cancer treatment. Here in our study, a versatile cancer cell membrane (CCM) coated calcium carbonate (CC) nanoparticles (MC) that capable of generating in situ tumor-associated antigens (TAAs) for DC vaccination is developed. Low-dose doxorubicin hydrochloride (Dox) could be encapsulated in the CC core of MC to trigger immunogenic cell death (ICD) while chlorins e6 (Ce6), a commonly adopted photosensitizer, was loaded in the CCM of MC for effective photodynamic therapy (PDT) through the generation of reactive oxygen species (ROS) to finally construct the vaccine (MC/Dox/Ce6). Most importantly, our in-depth study revealed the treatment of MC/Dox/Ce6 was able to elicit TAAs population and DC recruitment, triggering the following immune response cascade. In particular, the recruited DC cells could be stimulated in situ for effective vaccinations. Both in vitro and in vivo experiments suggested the capability of this all-in-one DDS to enhance DCs maturation to finally result in effective inhibition of both primary and distant growth of breast cancer upon single administration of low dose Dox and Ce6.