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树突状细胞/肿瘤细胞融合细胞膜纳米疫苗的研制及其在卵巢癌治疗中的应用。

Development of a Dendritic Cell/Tumor Cell Fusion Cell Membrane Nano-Vaccine for the Treatment of Ovarian Cancer.

机构信息

Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

出版信息

Front Immunol. 2022 Feb 17;13:828263. doi: 10.3389/fimmu.2022.828263. eCollection 2022.


DOI:10.3389/fimmu.2022.828263
PMID:35251013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8893350/
Abstract

Ovarian cancer (OC) is a malignant tumor that seriously affects women's health. In recent years, immunotherapy has shown great potential in tumor treatment. As a major contributor of immunotherapy, dendritic cells (DCs) - based tumor vaccine has been demonstrated to have a positive effect in inducing immune responses in animal experiments. However, the effect of tumor vaccines in clinical trials is not ideal. Therefore, it is urgent to improve the existing tumor vaccines for tumor treatment. Here, we developed a fusion cell membrane (FCM) nano-vaccine FCM-NPs, which is prepared by fusing DCs and OC cells and coating the FCM on the poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with the immune adjuvant CpG-oligodeoxynucleotide (CpG-ODN). The fusion process promoted the maturation of DCs, thus up-regulating the expression of costimulatory molecule CD80/CD86 and accelerating lymph node homing of DCs. Furthermore, FCM-NPs has both the immunogenicity of tumor cells and the antigen presenting ability of DCs, it can stimulate naive T lymphocytes to produce a large number of tumor-specific cytotoxic CD8 T lymphocytes. FCM-NPs exhibited strong immuno-activating effect both and . By establishing subcutaneous transplanted tumor model, patient-derived xenograft tumor model and abdominal metastatic tumor model, FCM-NPs was proved to have the effect of delaying the growth and inhibiting the metastasis of OC. FCM-NPs is expected to become a new tumor vaccine for the treatment of ovarian cancer.

摘要

卵巢癌(OC)是一种严重影响女性健康的恶性肿瘤。近年来,免疫疗法在肿瘤治疗中显示出巨大的潜力。作为免疫疗法的主要贡献者之一,基于树突状细胞(DCs)的肿瘤疫苗在动物实验中已被证明能诱导免疫反应。然而,肿瘤疫苗在临床试验中的效果并不理想。因此,迫切需要改进现有的肿瘤疫苗用于肿瘤治疗。在这里,我们开发了一种融合细胞膜(FCM)纳米疫苗 FCM-NPs,它是通过融合 DCs 和 OC 细胞并将 FCM 涂覆在负载免疫佐剂 CpG 寡脱氧核苷酸(CpG-ODN)的聚乳酸-共-羟基乙酸(PLGA)纳米颗粒(NPs)上制备的。融合过程促进了 DC 的成熟,从而上调了共刺激分子 CD80/CD86 的表达,并加速了 DC 的淋巴结归巢。此外,FCM-NPs 既有肿瘤细胞的免疫原性,又有 DC 的抗原提呈能力,它可以刺激幼稚 T 淋巴细胞产生大量的肿瘤特异性细胞毒性 CD8 T 淋巴细胞。FCM-NPs 在体内和体外均表现出强烈的免疫激活作用。通过建立皮下移植瘤模型、患者来源异种移植瘤模型和腹腔转移瘤模型,证明 FCM-NPs 具有延缓 OC 生长和抑制转移的作用。FCM-NPs 有望成为治疗卵巢癌的一种新的肿瘤疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/97ac1ee3c91e/fimmu-13-828263-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/86caa657f1c2/fimmu-13-828263-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/ca8c373dbcdc/fimmu-13-828263-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/73c5412651b1/fimmu-13-828263-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/fb96f67c0258/fimmu-13-828263-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/b926e61a7451/fimmu-13-828263-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/0363ec19951a/fimmu-13-828263-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/830813426182/fimmu-13-828263-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/97ac1ee3c91e/fimmu-13-828263-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/86caa657f1c2/fimmu-13-828263-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/ca8c373dbcdc/fimmu-13-828263-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/73c5412651b1/fimmu-13-828263-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/fb96f67c0258/fimmu-13-828263-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/b926e61a7451/fimmu-13-828263-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/0363ec19951a/fimmu-13-828263-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/830813426182/fimmu-13-828263-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b81a/8893350/97ac1ee3c91e/fimmu-13-828263-g008.jpg

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本文引用的文献

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Sci Rep. 2021-7-19

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Physiol Rep. 2021-1

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