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中国生物工程杂志

China Biotechnology
China Biotechnology  2021, Vol. 41 Issue (2/3): 78-88    DOI: 10.13523/j.cb.2011027
    
Research Progress and Application of Bispecific Nanobody
YUAN Bo1,2,WANG Jie-wen1,2,KANG Guang-bo1,2,HUANG He1,2,***()
1 Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China
2 Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin 300072, China
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Abstract  

This article reviews the application and advances of bispecific nanobodies from the research progress of nanobodies and studies of bispecific nanobodies in treating infectious diseases, cancer, and immune system diseases. Moreover, it highlights the research hotspots and potential research areas at this current stage. For in-depth analysis, the differences between nanobodies and full-length monoclonal antibodies are compared and the unique advantages of bispecific nanobodies are demonstrated. The research progress of nanobodies has been summarized, while emphasizing the research hot spots of neutralizing nanobodies of the COVID-19, CAR-T cell therapy, and immune checkpoint therapy antibodies. In conclusion, a prospect analysis of the application prospects of bispecific nanobodies is carried out. It is pointed out that bispecific nanobodies are able to overcome the shortcomings of full-length antibody and become a form of the antibody with great druggability.



Key wordsNanobody      Bispecific antibody      Infectious diseases      Tumor therapy      Immune diseases     
Received: 16 November 2020      Published: 08 April 2021
ZTFLH:  Q51  
Corresponding Authors: He HUANG     E-mail: huang@tju.edu.cn
Cite this article:

YUAN Bo,WANG Jie-wen,KANG Guang-bo,HUANG He. Research Progress and Application of Bispecific Nanobody. China Biotechnology, 2021, 41(2/3): 78-88.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2011027     OR     https://manu60.magtech.com.cn/biotech/Y2021/V41/I2/3/78

Fig.1 The different types of bispecific antibodies (a) The conventional full-length monoclonal antibody (b) The camelid heavy chain antibody (c) Single-chain fragment variable(scFv) antibody (d) Nanobody? or VHH (e) Bispecific nanobody (f)Bispecific nanobody KN046 (g) Bispecific T cell engagers
Fig.2 The application of bisspecific nanobodies in different treatment fields
抗体名称 靶标 治疗疾病 年份 参考文献
NbF12-10 AahI型毒素/AahII型毒素 Aah蝎子毒素 2010 [17]
ABA TcdA/TcdB 艰难梭状芽孢杆菌(CDI)感染 2014 [18]
T5-V36 TerC/Mac-1 破伤风毒素 2015 [19]
RTA-VHH-RTB-VHHs RTA/ RTB 蓖麻毒素 2015 [20]
JMN-D10-JMO-G1 水肿因子/致死因子 炭疽杆菌毒素感染 2016 [21]
Ad/VNA2-PA 水肿因子/致死因子 炭疽杆菌毒素感染 2016 [22]
NbF12-10 AahI型毒素/AahII型毒素 澳大利亚海蛇毒毒素 2018 [23]
ACE-Anti-CD16 VHH sACE22/CD16 新冠状病毒 2020 [24]
H11-D4/HH11-H4 RBD /ACE2 新冠状病毒 2020 [25]
NbPCV2 -NbcRBC PCV2/cRBCs 猪圆环2型病毒 2020 [26]
Table1 Anti-infectious diseases bispecific nanobodies
抗体名称 靶标 治疗疾病 年份 参考文献
IE2-AIb8/6E10-AIb8 HGF/HSA HGF表达肿瘤,如胶质瘤 2012 [32]
MaAbNA HER2/EGFR1 乳腺癌 2015 [33]
ttα GFP-α CEA
ttα GFP-α EGFR-α CEA
CEA/GFP/EGFR 人表皮样癌 2016 [34]
VHH EGFR-VHH GFP GFP/EGFR EGFR阳性肿瘤 2017 [35]
VHH CD3ε- VHH CD19 CD3ε/CD19 特异性表达CD19的肿瘤 2017 [36]
7D12-5GS-6H4 Vγ9Vδ2-T cells/EGFR Vγ9Vδ2-T cells的肿瘤
EGFR相关肿瘤
2017 [37]
ENb-TRAIL DR/EGFR 大肠癌、肺癌和胶质瘤 2017 [38]
RR2-H-RR4-Lip HER2表位1/ HER2表位2 乳腺癌 2018 [39]
Muc1-Bi-1 Muc1/CD16 Muc1细胞异常表达引发的多种癌症 2018 [40]
NanoCAR HER2/CD20 B细胞白血病和淋巴瘤 2018 [41]
PEG-S-Fab CEA/CD3 人结肠腺癌细胞治疗 2018 [42]
SBC77 CEA/CD16a CEA在不同恶性肿瘤中过度表达的治疗
(包括结肠直肠癌、胃癌、乳腺癌等)
2019 [43]
STAR-isolated Nb157 CD13/TIM3 急性髓系白血病 2020 [44]
Bi1/Bi2 FP/EGFR 肺癌、头颈癌和结肠癌等高表达EGFR的恶性肿瘤 2020 [45]
TSsdAb CD16/EGFR EGFR阳性肿瘤 2020 [46]
Table 2 Anti-tumor bispecific nanobodies
抗体名称 靶标 治疗疾病 年份 参考文献
Ozoralizumab(ATN-103) TNF-α/HSA 类风湿关节炎(RA) 2012 [15]
FAF Nb2-MSA21 Furin/MT1-MMP 胶溶蛋白淀粉样病变 2014 [68]
ALX-0061 IL-6/HSA 类风湿关节炎(RA) 2015 [16]
TROS TNFR/HSA 类风湿关节炎(RA)、克罗恩病(CD) 2015 [69]
AAV9-Nb11-FAF1 Furin/MT1-MMP 胶溶蛋白淀粉样病变 2017 [70]
M1095 IL-17A/IL-17F 银屑病 2017 [71]
Nb 70-alb-14 MMP8/hTNFR1 急性炎症和败血症 2018 [72]
VHH (J3/3E3)-VHH (2E7) gp41/gp120 获得性免疫缺陷综合征 2019 [73]
Everestmab GLP-1/GLP-1R T2DM(2型糖尿病) 2020 [74]
Table 3 Immune disease bispecific nanobodies
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