Virus-Like Nanotherapeutic for Spatiotemporally Enhancing Antigen Presentation and Cross-Presentation toward Potential Personalized Immunotherapy

One of the major causes of immunotherapy resistance is the loss of major histocompatibility complex class I (MHC-I) molecules in tumor cells or the downregulation of the class I antigen presentation pathway. In this study, a novel virus-like nanotherapeutic (siRNA@HCM) is developed via encapsulating...

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Veröffentlicht in:Advanced healthcare materials 2023-10, Vol.12 (26), p.e2300921-e2300921
Hauptverfasser: Li, Xiaodi, Yuan, Pengfei, Yang, Haiyuan, Zong, Xiaoqing, Yang, Caiqi, Chen, Xinjie, Li, Yuchao, Yan, Xiaodie, Wen, Yaoqi, Zhu, Tianci, Zhang, Qian, Xue, Wei, Dai, Jian
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Sprache:eng
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Zusammenfassung:One of the major causes of immunotherapy resistance is the loss of major histocompatibility complex class I (MHC-I) molecules in tumor cells or the downregulation of the class I antigen presentation pathway. In this study, a novel virus-like nanotherapeutic (siRNA@HCM) is developed via encapsulating nanosized siRNA nanoparticles in a hybrid membrane comprising a personalized tumor cell membrane and a universal 293T membrane expressing the mutant vesicular stomatitis virus glycoprotein (mVSV-G). Upon intravenous administration, siRNA@HCM accumulates at the tumor site and provides two potent driving forces for antitumor immunity. First, mVSV-G induces the fusion of siRNA@HCM with tumor cell membranes and directly injects siRNAs into the cytoplasm, significantly improving tumor intrinsic MHC-I antigen presentation. Moreover, mVSV-G can promote the maturation of dendritic cells, thereby achieving highly efficient antigen cross-presentation. The results demonstrate that spatiotemporally enhancing tumor intrinsic antigen presentation and cross-presentation via siRNA@HCM can achieve satisfactory antitumor efficacy and excellent biocompatibility. Immune infiltration analysis shows that siRNA@HCM treatment turns cold tumors into hot tumors. In addition, it significantly promotes the therapeutic effect of programmed death-1 inhibitor. In summary, virus-like nanotherapeutics present a promising approach to enhance the antitumor immune response, with distinct advantages for potential personalized therapy and clinical applications.
ISSN:2192-2640
2192-2659
DOI:10.1002/adhm.202300921