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基于源自癌细胞和树突状细胞的杂交细胞的细胞膜构建的可扩展免疫治疗性纳米平台。

Expandable Immunotherapeutic Nanoplatforms Engineered from Cytomembranes of Hybrid Cells Derived from Cancer and Dendritic Cells.

机构信息

Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.

The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, P. R. China.

出版信息

Adv Mater. 2019 May;31(18):e1900499. doi: 10.1002/adma.201900499. Epub 2019 Mar 25.

DOI:10.1002/adma.201900499
PMID:30907473
Abstract

Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co-stimulatory molecules for robust immunotherapy. FMs share the tumor's self-targeting character with the parent cancer cells. In bilateral tumor-bearing mouse models, the FM-coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post-nanophotosensitizer-induced photodynamic therapy (PDT). The FM-induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy-caused regression of the irradiation-free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor-specific immunotherapy-based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.

摘要

利用源自癌细胞和树突状细胞融合的细胞质膜(FM),本研究提供了一个基于生物学的平台,将免疫疗法与传统肿瘤治疗方法相结合。由于细胞融合所涉及的免疫激活,FM 可以有效地表达完整的癌症抗原和免疫协同刺激分子,从而进行有效的免疫治疗。FM 与亲本癌细胞共享肿瘤的自我靶向特征。在双侧荷瘤小鼠模型中,FM 涂层的纳米光敏剂可引起持久的免疫反应,以抑制纳米光敏剂诱导的光动力疗法(PDT)后原发性肿瘤的反弹。FM 诱导的免疫疗法显示出超高的抗肿瘤效果,甚至可与 PDT 相媲美。另一方面,对原发性肿瘤进行 PDT 可增强免疫疗法引起的未照射远处肿瘤的消退。因此,原发性和远处肿瘤几乎完全被消除。由于具有灵活的纳米颗粒选择,这种基于肿瘤特异性免疫疗法的纳米平台具有潜在的可扩展性,可适用于多种肿瘤类型,并可轻松配备多种功能。

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