RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Long-Acting In Situ Cancer Vaccines by Oncolytic STING-Activating Microgels.
Long-Acting In Situ Cancer Vaccines by Oncolytic STING-Activating Microgels.
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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。
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.
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