免疫系统
TLR9型
免疫疗法
抗原
癌症研究
抗体
癌症免疫疗法
癌症
免疫学
肿瘤微环境
癌细胞
CpG寡核苷酸
医学
生物
内科学
基因
基因表达
DNA甲基化
生物化学
作者
Idit Sagiv-Barfi,Debra K. Czerwinski,Shoshana Levy,Israt S. Alam,Aaron T. Mayer,Sanjiv S. Gambhir,Ronald Levy
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2018-01-31
卷期号:10 (426)
被引量:309
标识
DOI:10.1126/scitranslmed.aan4488
摘要
It has recently become apparent that the immune system can cure cancer. In some of these strategies, the antigen targets are preidentified and therapies are custom-made against these targets. In others, antibodies are used to remove the brakes of the immune system, allowing preexisting T cells to attack cancer cells. We have used another noncustomized approach called in situ vaccination. Immunoenhancing agents are injected locally into one site of tumor, thereby triggering a T cell immune response locally that then attacks cancer throughout the body. We have used a screening strategy in which the same syngeneic tumor is implanted at two separate sites in the body. One tumor is then injected with the test agents, and the resulting immune response is detected by the regression of the distant, untreated tumor. Using this assay, the combination of unmethylated CG-enriched oligodeoxynucleotide (CpG)-a Toll-like receptor 9 (TLR9) ligand-and anti-OX40 antibody provided the most impressive results. TLRs are components of the innate immune system that recognize molecular patterns on pathogens. Low doses of CpG injected into a tumor induce the expression of OX40 on CD4+ T cells in the microenvironment in mouse or human tumors. An agonistic anti-OX40 antibody can then trigger a T cell immune response, which is specific to the antigens of the injected tumor. Remarkably, this combination of a TLR ligand and an anti-OX40 antibody can cure multiple types of cancer and prevent spontaneous genetically driven cancers.
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