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磁性雕塑样肿瘤细胞疫苗可实现靶向免疫激活并产生强大的抗肿瘤效果。

Magnetic sculpture-like tumor cell vaccines enable targeted immune activation and potent antitumor effects.

作者信息

Zhang Heng, Li Qing-Qing, Shi Yue, Zhang Lei, Wang Kai-Wen, Wu Ting, Cheng Shan-Bin, Zhang Zi-Ren, Qin Lu-Ning, Zhao Yun-Long, Zhen Xue-Ting, Ren Hao-Ran, Du Lin-Yong, Liu Hui-Juan, Sun Tao

机构信息

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.

Tianjin International Joint Academy of Biomedicine, Tianjin, China.

出版信息

Theranostics. 2025 Apr 13;15(11):5358-5380. doi: 10.7150/thno.107162. eCollection 2025.

DOI:10.7150/thno.107162
PMID:40303352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12036876/
Abstract

Tumor cells are ideal candidates for developing cancer vaccines due to their antigenic profiles, yet existing whole-cell vaccines lack efficacy. This study aimed to develop a novel whole-cell vaccine platform that combines immunogenicity, structural integrity, and tumor-targeting capabilities. We created "Magnetic Sculpture-like (MASK) Cells" by treating tumor cells with high-concentration FeCl, inducing rapid morphological fixation without traditional chemical crosslinking. MASK cells were characterized for proliferative capacity, biomolecule retention, and magnetic properties. Vaccine efficacy was tested , in melanoma-bearing mouse models, and through spatial transcriptomic profiling of tumor microenvironments. Combination therapy with anti-PD-1 was further evaluated. MASK cells lose proliferative ability but retain biomolecules and architecture. MASK cells promote dendritic cell maturation and T cell responses against tumors. Vaccines combining MASK cells and adjuvant potently suppress melanoma growth. Uniquely, FeCl sculpting imparts magnetism to cells, enabling directional navigation to tumors using magnetic fields and enhanced immune activation. Spatial transcriptomics reveals DC and T cell activation and tumor cytotoxicity after MASK vaccination. Combined with anti-PD-1, MASK cell vaccines strongly inhibit growth and improve survival. MASK cells represent a promising new approach for targeted, patient-specific anti-tumor therapeutics.

摘要

由于肿瘤细胞的抗原特性,它们是开发癌症疫苗的理想候选者,但现有的全细胞疫苗缺乏疗效。本研究旨在开发一种结合免疫原性、结构完整性和肿瘤靶向能力的新型全细胞疫苗平台。我们通过用高浓度氯化铁处理肿瘤细胞,诱导快速形态固定,无需传统化学交联,从而创建了“磁雕样(MASK)细胞”。对MASK细胞的增殖能力、生物分子保留和磁性进行了表征。在荷黑素瘤小鼠模型中,并通过肿瘤微环境的空间转录组分析来测试疫苗疗效。进一步评估了与抗PD-1的联合治疗。MASK细胞失去增殖能力,但保留生物分子和结构。MASK细胞促进树突状细胞成熟和针对肿瘤的T细胞反应。将MASK细胞与佐剂结合的疫苗能有效抑制黑素瘤生长。独特的是,氯化铁雕刻赋予细胞磁性,使其能够利用磁场定向导航到肿瘤部位并增强免疫激活。空间转录组学揭示了MASK疫苗接种后树突状细胞和T细胞的激活以及肿瘤细胞毒性。与抗PD-1联合使用时,MASK细胞疫苗能强烈抑制肿瘤生长并提高生存率。MASK细胞代表了一种有前景的新方法,用于靶向、针对患者的抗肿瘤治疗。

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本文引用的文献

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Self-Metallized Whole Cell Vaccines Prepared by Microfluidics for Bioorthogonally Catalyzed Antitumor Immunotherapy.微流控技术制备自金属化全细胞疫苗用于生物正交催化抗肿瘤免疫治疗。
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Rethinking Antigen Source: Cancer Vaccines Based on Whole Tumor Cell/tissue Lysate or Whole Tumor Cell.重新思考抗原来源:基于全肿瘤细胞/组织裂解物或全肿瘤细胞的癌症疫苗。
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