肿瘤微环境
免疫检查点
免疫疗法
免疫系统
细胞毒性T细胞
抗体
封锁
光动力疗法
化学
癌症研究
医学
免疫学
体外
受体
内科学
有机化学
生物化学
作者
Dangge Wang,Tingting Wang,Haijun Yu,Bing Feng,Lei Zhou,Fangyuan Zhou,Bo Hou,Hanwu Zhang,Min Luo,Yaping Li
出处
期刊:Science immunology
[American Association for the Advancement of Science]
日期:2019-07-05
卷期号:4 (37)
被引量:215
标识
DOI:10.1126/sciimmunol.aau6584
摘要
Immunological tolerance of tumors is characterized by insufficient infiltration of cytotoxic T lymphocytes (CTLs) and immunosuppressive microenvironment of tumor. Tumor resistance to immune checkpoint inhibitors due to immunological tolerance is an ongoing challenge for current immune checkpoint blockade (ICB) therapy. Here, we report the development of tumor microenvironment-activatable anti-PDL1 antibody (αPDL1) nanoparticles for combination immunotherapy designed to overcome immunological tolerance of tumors. Combination of αPDL1 nanoparticle treatment with near-infrared (NIR) laser irradiation-triggered activation of photosensitizer indocyanine green induces the generation of reactive oxygen species, which promotes the intratumoral infiltration of CTLs and sensitizes the tumors to PDL1 blockade therapy. We showed that the combination of antibody nanoparticles and NIR laser irradiation effectively suppressed tumor growth and metastasis to the lung and lymph nodes in mouse models. The nanoplatform that uses the antibody nanoparticle alone both for immune stimulation and PDL1 inhibition could be readily adapted to other immune checkpoint inhibitors for improved ICB therapy.
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