肿瘤微环境
免疫疗法
癌症研究
免疫系统
癌症免疫疗法
免疫抑制
自愈水凝胶
医学
免疫学
化学
有机化学
作者
Chao Wan,Yajie Sun,Yan Hu,Jing Huang,Lisen Lu,Yanan Gao,Huaduan Zi,Qianyuan He,Jinfeng Sun,Jonathan F. Lovell,Kunyu Yang,Jin Huang
出处
期刊:Nano Today
[Elsevier]
日期:2021-12-01
卷期号:41: 101323-101323
被引量:16
标识
DOI:10.1016/j.nantod.2021.101323
摘要
In advanced stage patients, traditional cancer chemotherapies often demonstrate limited tumor growth inhibition and fail to elicit sufficient anti-tumor immunity required for long-lasting responses. Herein, we developed a therapeutic peptide hydrogel manufactured using a PEG cross-linked melittin-peptide scaffold that not only itself induces tumor cell killing, but also encapsulates the processed cell secretions of autologous, irradiated tumor cells. MLT-RADA-Polyethylene glycol (MRP) loaded with the concentrated ultrafiltration (UF) retentate from irradiated tumor cell media, denoted as [email protected] effectively reshapes the tumor microenvironment (TME) by stimulating dendritic cell maturation and reprogramming macrophages toward a tumoricidal M1 phenotype. In multiple murine tumor models, in which immune checkpoint blockade (ICB) alone did not control advanced disease, intratumoral administration of [email protected] enhanced ICB efficacy, leading to prolonged survival. The combination of [email protected] and ICB appears to be an effective approach to rapidly kill tumor cells, diminish immunosuppression in the TME, and activate host adaptive immune responses, all of which work in concert in an immunotherapy regime to control established and aggressive tumors.
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