ZHANG Juan and HUANG Zhangjian Report on the New Progress of Anti-hepatocarcinoma Research by Antibody-nitric Oxide Conjugate

Release date:2019-04-18  Release:主页英文版

   


Recently, Cancer Research (influence factor 9.130), the authoritative journal of the field of oncology, published the latest research results jointly reported by Associate Professor ZHANG Juan of the School of Life Science and Technology and Researcher HUANG Zhangjian of the Institute of Pharmaceutical Sciences——Anti-CD24 antibody-nitric oxide conjugate (ANC) selectively and potently suppresses hepatic carcinoma. Ph.D. student SUN Fumou in Microbiology and Biochemical Pharmacy is the first author of this article. Associate Professor ZHANG Juan and Researcher HUANG Zhangjian are correspondent authors of this article.


Traditional antibody-drug conjugates (ADC) are made by coupling a chemical with a strong cytotoxic chemical via a linker to a monoclonal antibody, which combines the powerful lethality of small molecule drugs with the high degree of targeting of monoclonal antibodies. Inspired by the ADC design, ZHANG Juan team and HUANG Zhangjian team successfully achieved the targeted delivery of the gas messenger molecule nitric oxide (NO) through the monoclonal antibody, and proposed the antibody nitric oxide conjugate (antibody nitric oxide conjugate, ANCfor the first time. It provides a new design idea for the development of anti-tumor drugs.


NO has broad application prospects in tumor treatment, and how to accurately deliver it to cancer lesions becomes a bottleneck restricting its drug-forming properties. ADC drugs have made breakthroughs in the field of solid tumors and hematoma treatments in recent years. However, studies of traditional ADC have focused on the use of antibodies to deliver highly toxic small molecules such as tubulin inhibitors, while at the same time providing high toxic side effects. The team of ZHANG Juan and HUANG Zhangjian broadened the concept of ADC drug, and skillfully combined the anti-CD24 mAb developed by the team with the NO donor to connect with the antibody by using a disulfide bond that is broken in the redox environment of the tumor lesion. An antibody nitric oxide conjugate (ANC) was obtained. The ANC binds to the specific receptor molecule CD24, which is highly expressed on the surface of liver cancer cells, and enters the liver cancer cells by endocytosis mediated by CD24 molecules. The disulfide bond cleavage then releases the high concentration of NO. Molecules to achieve selective killing of tumor cells.


The ANC small-scale production process is controllable. It has the advantages of selective tumor targeting, clear mechanism of action, stable circulation in vivo, remarkable pharmacodynamic effect and extremely low toxic and side effects, and can also be used for other tumors with high CD24 expression such as colorectal cancer, head and neck cancer, ovarian cancer, etc.


This research has expanded the design concept of ADC and proposed the concept of ANC for the first time to solve the problem of NO targeted drug delivery. The design concept of the ANC can be extended to the development of more gas small molecule drugs with therapeutic potential. At present, the ANC has applied for Chinese patents and international patents, which has good application and transformation prospects. This achievement was also reported as a recent research hot spot by the scientific review journal Hepatic Cell News (Volume 3.11 | Mar 29).

  

The research was supported by the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, and the Double-Class Construction Project of China Pharmaceutical University.