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FZD7多肽疫苗的抗肿瘤作用及机制

Antitumor effect and mechanism of FZD7 polypeptide vaccine.

作者信息

Hua Zhongke, Han Yu, Liu Kan, Yang Hua, Zhou Cai, Chen Fengyi, Nie Shenglan, Li Mengqing, Yu Qinyao, Wei Yunpeng, Wu Christina C N, Wang Xiaomei

机构信息

International Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.

Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.

出版信息

Front Oncol. 2022 Oct 5;12:925495. doi: 10.3389/fonc.2022.925495. eCollection 2022.

Abstract

The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). and vitro tests were used to assess tumor cell inhibition. , the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response and , and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.

摘要

放疗和化疗后增殖的耐药细胞主要是具有高干细胞标志物表达的肿瘤干细胞,它们的存在是肿瘤扩散的主要原因。Wnt信号受体卷曲蛋白家族受体7(FZD7)与干细胞特征的维持以及癌症进展有关。卷曲蛋白-7(FZD7)是Wnt/β-连环蛋白信号的关键受体,在三阴性乳腺癌(TNBC)中过表达,这表明它可能是癌症治疗的一个可行靶点。我们利用生物信息学来寻找得分最高的肽,化学合成FZD7表位抗原,并结合Toll样受体7激动剂(T7)。在良好生产规范(GMP)条件下,生产并纯化了用于疫苗的肽(>95%)。并通过体外试验评估肿瘤细胞抑制情况。此外,FZD7-T7疫苗可显著提高骨髓来源树突状细胞(BMDC)的成熟度。在小鼠中,FZD7-T7疫苗引发了最强的免疫反应。在预防实验中,用FZD7-T7处理的BALB/c小鼠出现了显著的肿瘤生长抑制(P<0.01)。在接种FZD7-T7的小鼠中,多种促进细胞免疫反应的细胞因子,如干扰素(IFN)-γ(P<0.05)、白细胞介素(IL)-12(P<0.05)和IL-2(P<0.01)显著升高。此外,我们从疫苗成分方面评估了安全性问题,以帮助开发成功的下一代疫苗。总之,FZD7-T7疫苗可以激活免疫反应并发挥肿瘤抑制作用。我们的研究结果揭示了FZD7肽在TNBC中独特的肿瘤抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f675/9579692/404bcd370584/fonc-12-925495-g006.jpg

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