免疫系统
癌细胞
癌症研究
细胞毒性T细胞
癌症
癌症免疫疗法
化学
病毒载体
免疫疗法
遗传增强
基因
分子生物学
生物
免疫学
重组DNA
生物化学
体外
遗传学
作者
Amit Fischer,Avner Ehrlich,Yevgeni Plotkin,Yu Ouyang,Klil Asulin,Konstantinos Ioannidis,Chunhai Fan,Yaakov Nahmias,Itamar Willner
标识
DOI:10.1002/anie.202311590
摘要
The combination of gene therapy and immunotherapy concepts, along recent advances in DNA nanotechnology, have the potential to provide important tools for cancer therapies. We present the development of stimuli-responsive microcapsules, loaded with a viral immunogenetic agent, harnessing the immune response against the Coronavirus Disease 2019, COVID-19, to selectively attack liver cancer cells (hepatoma) or recognize breast cancer or hepatoma, by expression of green fluorescence protein, GFP. The pH-responsive microcapsules, modified with DNA-tetrahedra nanostructures, increased hepatoma permeation by 50 %. Incorporation of a GFP-encoding lentivirus vector inside the tumor-targeting pH-stimulated miRNA-triggered and Alpha-fetoprotein-dictated microcapsules enables the demonstration of neoplasm selectivity, with approximately 5,000-, 8,000- and 50,000-fold more expression in the cancerous cells, respectively. The incorporation of the SARS-CoV-2 spike protein in the gene vector promotes specific recognition of the immune-evading hepatoma by the COVID-19-analogous immune response, which leads to cytotoxic and inflammatory activity, mediated by serum components taken from vaccinated or recovered COVID-19 patients, resulting in effective elimination of the hepatoma (>85 % yield).
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