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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (6): 69-75    DOI: 10.13523/j.cb.2301003
综述     
疟原虫重组蛋白rVAR2及其在肿瘤靶向治疗中的应用进展*
蒋金露1,2,潘海峰2,3,于思远2,3,李廷栋2,3,葛胜祥2,3,**()
1 厦门大学生命科学学院 厦门大学国家传染病诊断试剂与疫苗工程技术研究中心 厦门 361102
2 厦门大学公共卫生学院 厦门大学分子疫苗学和分子诊断学国家重点实验室 厦门 361102
3 医用生物制品省部共建协同创新中心 厦门 361102
Recombinant Malaria Protein rVAR2 and Its Application in Tumor-targeted Therapy
JIANG Jin-lu1,2,PAN Hai-feng2,3,YU Si-yuan2,3,LI Ting-dong2,3,GE Sheng-xiang2,3,**()
1 School of Life Science, National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen 361102, China
2 Department of Laboratory Medicine, School of Public Health, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen 361102, China
3 Collaborative Innovation Center of Biological Products, Xiamen University, Xiamen 361102, China
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摘要：

恶性肿瘤是造成人类死亡的主要原因之一,其发病率和死亡率逐年上升。靶向药物可精确作用于肿瘤,在近年来备受关注。特异性识别和广泛结合肿瘤细胞是实现肿瘤靶向治疗的关键,而目前缺乏高效特异的泛肿瘤靶向工具,这极大地限制了肿瘤靶向治疗的进一步发展。与现有的肿瘤靶向方式相比,疟原虫重组蛋白rVAR2能够特异性结合肿瘤细胞表面广泛表达的癌胚硫酸软骨素(oncofetal chondroitin sulfate,ofCS),具备泛肿瘤靶向的优点,为肿瘤靶向治疗提供了新思路。对rVAR2的特点及其近年来在肿瘤靶向治疗中的应用进展进行分析和总结,并对其未来发展方向进行了展望,以期为临床肿瘤靶向治疗及诊断方法的发展提供参考。
关键词： VAR2CSA;  rVAR2;  硫酸软骨素;  癌胚硫酸软骨素;  肿瘤靶向    
Abstract:

Malignant tumor is considered to be one of the main causes of human death, and its morbidity and mortality are increasing by years. Tumor-targeted drugs can act precisely on tumors and have gained a lot of attention in recent years. Specific identification and extensive binding to tumor cells are key to achieving tumor-targeted therapy, and the lack of effective and specific pan-tumor targeting tools has greatly limited the further development of tumor-targeted therapy. Compared with existing tumor targeting approaches, Plasmodium recombinant protein rVAR2 can specifically bind Oncofetal chondroitin sulfate (ofCS), which is widely expressed on the surface of tumor cells, and has the advantage of pan-tumor targeting, providing a new idea for tumor targeting therapy. In this paper, we analyze and summarize the characteristics of rVAR2 and its progress in tumor-targeted therapy in recent years, and discuss its future development direction, in order to provide a reference for the development of clinical tumor-targeted therapy and diagnosis methods.
Key words: VAR2CSA    rVAR2    Chondroitin sulfate    Oncofetal chondroitin sulfate (ofCS)    Tumor targeting
收稿日期: 2023-01-03 出版日期: 2023-07-04
ZTFLH:  Q819  
基金资助: * 国家自然科学基金(31971369);国家自然科学基金(82204459)
通讯作者: **电子信箱:sxge@xmu.edu.cn   
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蒋金露
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引用本文:

蒋金露, 潘海峰, 于思远, 李廷栋, 葛胜祥. 疟原虫重组蛋白rVAR2及其在肿瘤靶向治疗中的应用进展*[J]. 中国生物工程杂志, 2023, 43(6): 69-75.

JIANG Jin-lu, PAN Hai-feng, YU Si-yuan, LI Ting-dong, GE Sheng-xiang. Recombinant Malaria Protein rVAR2 and Its Application in Tumor-targeted Therapy. China Biotechnology, 2023, 43(6): 69-75.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2301003    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I6/69

图1  VAR2CSA蛋白及重组蛋白rVAR2的示意图
图2  rVAR2蛋白可结合胎盘和肿瘤细胞表面特异性表达的CSA
肿瘤靶向元件 靶向原理 优势 局限性 参考文献
iRGD 识别并结合血管整合素 血管整合素在肿瘤组织部位高表达;能够内化到细胞中 由于血管整合素在其他组织广泛表达,iRGD靶向肿瘤的特异性有限 [45-46,48 -49]
抗体 结合肿瘤相关抗原 高特异性和高亲和力 由于肿瘤异质性,抗体靶向的通用性有限 [13,50]
环境响应型元件 根据环境生物化学特性(pH值、温度等)进行靶向 种类多样化 通用性有限;难以大规模制备 [51?-53]
核酸适配体 靶向肿瘤细胞膜上的高表达蛋白质 高特异性和高亲和力 体内稳定性差;存在安全性问题 [54?-56]
rVAR2 识别并结合肿瘤细胞表面的癌胚硫酸软骨素 癌胚硫酸软骨素在肿瘤中表达广泛,rVAR2与其结合具有高特异性;能够内化到细胞中 分子量大;内吞小泡逃逸效率低 [36,57]
表1  不同肿瘤靶向元件的比较
应用 细胞或肿瘤模型 参考文献
rVAR2偶联白喉毒素(DT388) 小鼠黑色素瘤细胞(B16-F10),人前列腺癌细胞(PC-3)荷瘤模型 [36]
rVAR2偶联哈米特林(Hemiasterlin)类似物(KT886) 小鼠乳腺癌细胞(4T1),人间变性大细胞淋巴瘤细胞(Karpas 299)荷瘤模型,人前列腺癌细胞(PC-3)荷瘤模型,人膀胱癌细胞(UM-UC13)荷瘤模型等 [36,58]
rVAR2偶联单甲基耳他汀E(MMAE) 人非小细胞肺癌细胞(A549)及其荷瘤模型 [59]
rVAR2偶联抗CD3抗体 人膀胱移行癌细胞(UM-UC-3)及其荷瘤模型 [60]
rVAR2修饰及血小板膜包被的纳米颗粒(rVAR2-PM /PLGA-ss-HA) 小鼠黑色素瘤细胞(B16- F10)及其荷瘤模型 [61]
表2  rVAR2蛋白在肿瘤靶向治疗中的应用
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