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溶瘤 STING 激活微凝胶长效原位癌症疫苗

英文原题:Long-Acting In Situ Cancer Vaccines by Oncolytic STING-Activating Microgels.

查看英文原题

Long-Acting In Situ Cancer Vaccines by Oncolytic STING-Activating Microgels.

PubMed 2025/08/05(内容时间) Small Q1 · IF 11.8(JCR 2025)

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中文摘要

利用肿瘤内源性多重抗原直接激发广泛免疫应答的原位癌症疫苗在肿瘤治疗中具有巨大潜力。然而,微弱的抗原呈递和不利的免疫微环境对获得临床获益构成了严峻挑战。在此,我们开发了溶瘤STING激活微凝胶(OSAM),可持续释放溶瘤肽LTX-315和STING佐剂diABZI(>4周),从而激发长效且强大的抗肿瘤免疫。OSAM诱导MHC I显著上调以及树突状细胞大幅活化超过一周。单次瘤内注射OSAM显著促进细胞毒性T淋巴细胞和NK 细胞的浸润,与抗CTLA-4微凝胶联合使用在多种不同小鼠肿瘤模型中取得了优异的治疗获益,治愈率达40%-71%。这些溶瘤STING激活微凝胶为原位癌症疫苗引入了一种新的强大策略。

展开英文摘要原文

In situ cancer vaccines exploiting endogenous multiple antigens directly from tumors to elicit broad immune responses hold great potential in cancer treatment.

However, the feeble antigen presentation and hostile immune microenvironments pose severe challenges to acquiring clinical benefits.

Here, oncolytic STING-activating microgels (OSAM) that release oncolytic peptide LTX-315 and STING adjuvant diABZI in a sustained manner (>4 weeks) have been developed to elicit long-acting and powerful antitumor immunity. OSAM induced significant upregulation of MHC I and substantial activation of dendritic cells for more than one week.

One single intratumoral administration of OSAM markedly promoted the infiltration of cytotoxic T lymphocytes and natural killer cells, which combining with anti-CTLA-4 microgels afforded exceptional therapeutic benefits in several different murine tumor models with a cure rate of 40%-71%. These oncolytic STING-activating microgels introduce a new and powerful strategy to in situ cancer vaccines.

论文信息

作者
Tan H、Guo J、Wang Y、Chen W、Zhong Z、Deng C
单位
Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Materials, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China.China
文献类型
非美国政府资助研究
期刊
Small (Weinheim an der Bergstrasse, Germany)2025 Sep
原文标识
PubMed 40761011 · DOI 10.1002/smll.202503561