主题:【分享】CD93:肿瘤血管生产和免疫浸润调控因子

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前  言

CD93是一种跨膜糖蛋白,在多种癌症的肿瘤血管中表达上调,与各种癌症的预后较差相关。在基础研究方面,2021年董晨研究团队首次鉴定CD93是IL-17D的功能性受体。同年,陈列平团队发现阻断CD93/IGFBP7通路可重塑脉管系统,增强免疫治疗效果。目前,CD93已成为免疫治疗领域的热门靶点之一。

01 CD93:生理学和病理学

CD93在内皮细胞、单核细胞、巨噬细胞、血小板和一些干细胞上表达,并且参与各种生理过程,如血管生成、细胞骨架动力学、内皮细胞的迁移和粘附、细胞凋亡和细胞外基质(ECM)重塑等。此外,CD93是一种基本的肿瘤血管生成调节因子。血管生成异常会导致肿瘤缺氧、pH降低和肿瘤微环境(TME)药物渗透性降低,促进肿瘤的生长和扩散。CD93还在TME和免疫浸润过程中发挥着关键作用。CD93可作为多种恶性肿瘤的预后生物标志物,可能是一个理想的治疗靶点。

2021年清华大学董晨院士团队在Immunity发表题为:Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93 的研究论文,首次鉴定了IL-17D的功能性受体为CD93,并揭示IL-17D通过结合CD93调节ILC3细胞的功能并参与维持肠道稳态。

CD93是IL-17D的功能性受体(图片源自https://doi.org/10.1016/j.immuni.2021.03.018)



02 CD93:临床研究进展

CD93直接与细胞外基质糖蛋白MMRN2相互作用,可控制内皮细胞动力学。阻断CD93与MMRN2之间的相互作用可能会损害肿瘤中的血管完整性,为药物治疗提供理想靶点。通过将免疫治疗与其他形式的治疗相结合来增强抗肿瘤反应,这一策略受到越来越多人的关注。近期研究表明,阻断CD93通路可以增强肿瘤血管功能、增加T细胞浸润和抗肿瘤免疫,使肿瘤对免疫-检查点阻断剂(ICB)治疗的反应性更强。截至2023年6月,有两种抗CD93单克隆抗体候选药物DCBY02和DCSZ11正处于临床试验阶段。

临床试验中的CD93靶向药物列表

药物药物类型靶点适应证临床阶段
DCBY02单克隆抗体CD93实体瘤I期
DCSZ11单克隆抗体CD93实体瘤I期

来源:https://clinicaltrials.gov



03 CD93:助力文章发表

义翘神州的CD93抗体已用于多种研究用途,包括在流式细胞术(FCM)中测量蛋白-配体结合。

2021年,科罗拉多大学Zhu yuwen课题组和耶鲁大学陈列平课题组在Science Translational Medicine期刊上发表研究成果,发现阻断CD93/IGFBP7通路可以重塑脉管系统(vasculature),改善药物递送到肿瘤微环境的效果,增强抗肿瘤药物的治疗效果。此外,阻断CD93通路还增加肿瘤微环境的效应T细胞,增强免疫治疗的效果。

本研究发现加入人抗CD93单抗(货号:12589-MM01,义翘神州)或抗IGFBP7单抗(货号:13100-R003,义翘神州)可显著降低IGFBP7蛋白与CD93转染的HEK293T细胞的结合,而这种相互作用对异常肿瘤血管的形成至关重要。

流式细胞术检测结果



A:在加入抗CD93单抗(货号:12589-MM01,义翘神州)或抗IGFBP7 单抗的情况下,用IGFBP7-Ig(货号:13100-R003,义翘神州)染色对照品或CD93构建体(分别为红色和蓝色)转染的HEK293T细胞,以进行结合。B:加入或不加入CD93的情况下,用对照品或IGFBP7-Ig(分别为红色和蓝色)染色HUVEC细胞。https://doi.org/10.1126/scitranslmed.abc8922

?义翘神州CD93明星产品

义翘神州的产品已支持多篇文章发表在国内外学术期刊,涉及到的产品有重组蛋白、抗体、ELISA试剂、基因等。

· Human CD93 Protein (His Tag), HPLC-verified (Cat: 12589-H08H)

Immobilized human CD93 (His Tag) can bind human IGFBP7.



· Mouse CD93 Protein (hFc Tag), HPLC-verified (Cat: 50759-M02H)



Immobilized human IGFBP7 / IBP-7 protein can bind mouse CD93 protein.

· Anti-CD93 Antibody (APC), Mouse Monoclonal (Cat: 12589-MM01-A)



Flow cytometric analysis of Human CD93 expression on monocytes in whole blood. Staining performed with APC-conjugated anti-Human CD93. Fluorescence histograms were generated using gated viable monocyte events based on forward and side light-scatter characteristics.

· Anti-CD93 Antibody, Rabbit Polyclonal (Cat: 106891-T08)



Mouse spleen was immunochemically stained with CD93 rabbit polyclonal antibody at 1:1000 dilution using formalin-fixed paraffin embedded sections.

更多CD93重组蛋白产品

货号种属-表达宿主标签纯度,活性
12589-H02HHuman-HEK293hFc>85%, Active
90995-K08HRhesus-HEK293His≥95%☆
80207-R08HRat-HEK293His>95%
50759-M08HMouse-HEK293His>90%


注:☆表示SEC-HPLC检测纯度

【参考文献】

1.S. Fantone et al. CD93 a potential player in cytotrophoblast and endothelial cell migration.  Cell and Tissue Research, 2021, doi: 10.1007/s00441-021-03543-3.

2.X. Zheng et al. CD93 orchestrates the tumor microenvironment and predicts the molecular subtype and therapy response of bladder cancer. Computers in Biology and Medicine, 2022, doi: 10.1016/j.compbiomed.2022.105727.

3. Greenlee-Wacker MC, et al. Membrane-associated CD93 regulates leukocyte migration and C1q-hemolytic activity during murine peritonitis. J Immunol 2011.

4. Kaiming Ma, et al. CD93 is Associated with Glioma?related Malignant Processes and Immunosuppressive Cell Infiltration as an Inspiring Biomarker of Survivance. Journal of Molecular Neuroscience, 2022. doi: 10.1007/s12031-022-02060-4

5. R. Lugano et al. CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis. Journal of Clinical Investigation, 2018. doi: 10.1172/jci97459.

6. Huang, et al. Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93. Immunity, 2021. https://doi.org/10.1016/j.immuni.2021.03.018

7. Y. Sun et al. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy. Science Translational Medicine, 2021. doi: 10.1126/scitranslmed.abc8922.

8. F. Galvagni et al. Dissecting the CD93-Multimerin 2 interaction involved in cell adhesion and migration of the activated endothelium. Matrix Biology, 2017. doi: 10.1016/j.matbio.2017.08.003.

9. Z. Zhang, et al. CD93 Correlates With Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis. Frontiers in Cell and Developmental Biology, 2022. doi: 10.3389/fcell.2022.817965.

10. clinicaltrials.gov. (n.d.). CD93 clinical trials. Retrieved June 30, 2023, from https://clinicaltrials.gov/search?term=CD93&viewType=Table&aggFilters=phase:1&checkSpell=false
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