癌症研究
肿瘤微环境
免疫检查点
免疫系统
细胞毒性T细胞
T细胞
靶向治疗
封锁
免疫学
免疫疗法
医学
癌症
生物
受体
内科学
体外
生物化学
作者
Manman Zhu,Yongjian Wu,Tianchuan Zhu,Jian Chen,Zhenxing Chen,Hanxi Ding,Siyi Tan,Jianzhong He,Qi Zeng,Xi Huang
标识
DOI:10.1158/2326-6066.c.7380062
摘要
<div>Abstract<p>The effectiveness of immune checkpoint inhibitor (ICI) therapy is hindered by the ineffective infiltration and functioning of cytotoxic T cells and the immunosuppressive tumor microenvironment (TME). Signaling lymphocytic activation molecule family member 7 (SLAMF7) is a pivotal co-stimulatory receptor thought to simultaneously trigger NK-cell, T-cell, and macrophage antitumor cytotoxicity. However, the potential of this collaborative immune stimulation in antitumor immunity for solid tumors is underexplored due to the exclusive expression of SLAMF7 by hematopoietic cells. Here, we report the development and characterization of multifunctional bispecific nanovesicles (NVs) targeting SLAMF7 and glypican-3—a hepatocellular carcinoma (HCC)–specific tumor antigen. We found that by effectively “decorating” the surfaces of solid tumors with SLAMF7, these NVs directly induced potent and specific antitumor immunity and remodeled the immunosuppressive TME, sensitizing the tumors to programmed cell death protein 1 (PD1) blockade. Our findings highlight the potential of SLAMF7-targeted multifunctional bispecific NVs as an anticancer strategy with implications for designing next-generation targeted cancer therapies.</p></div>
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