Shin Heejun, Na Kun
Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, Bucheon-si, Gyeonggi do 14662, Republic of Korea.
Department of Biomedical-Chemical Engineering, The Catholic University of Korea, Bucheon-si, Gyeonggi do 14662, Republic of Korea.
ACS Biomater Sci Eng. 2020 Jun 8;6(6):3430-3439. doi: 10.1021/acsbiomaterials.0c00379. Epub 2020 May 20.
A cancer vaccine is a promising immunotherapy modality, but the heterogenicity of tumors and substantial time and costs required in tumor-associated antigen (TAA) screening have hindered the development of an individualized vaccine. Herein, we propose vaccination using cancer-targetable pH-sensitive zinc-based immunomodulators (CZIs) to elicit antitumor immune response against TAAs of patients' tumors without the identification processes. In the tumor microenvironment, CZIs promote the release of large amounts of TAAs and exposure of calreticulin on the cell surface via immunogenic cell death through the combined effect of excess zinc ions and photodynamic therapy (PDT). With these properties, CZIs potentiate antitumor immunity and inhibit tumor growth as well as lung metastasis in CT26 tumor-bearing mice. This nanoplatform may suggest an alternative therapeutic strategy to overcoming the limitations of existing cancer vaccines and may broaden the application of nanoparticles for cancer immunotherapy.
癌症疫苗是一种很有前景的免疫治疗方式，但肿瘤的异质性以及肿瘤相关抗原（TAA）筛选所需的大量时间和成本阻碍了个性化疫苗的开发。在此，我们提出使用可靶向癌症的pH敏感锌基免疫调节剂（CZIs）进行疫苗接种，以在无需识别过程的情况下引发针对患者肿瘤TAA的抗肿瘤免疫反应。在肿瘤微环境中，CZIs通过过量锌离子和光动力疗法（PDT）的联合作用，通过免疫原性细胞死亡促进大量TAA的释放以及钙网蛋白在细胞表面的暴露。凭借这些特性，CZIs可增强抗肿瘤免疫力，并抑制CT26荷瘤小鼠的肿瘤生长以及肺转移。这种纳米平台可能为克服现有癌症疫苗的局限性提供一种替代治疗策略，并可能拓宽纳米颗粒在癌症免疫治疗中的应用。
