Recent advances of conditionally active antibodies
10.16438/j.0513-4870.2024-0071
- VernacularTitle:条件性激活抗体的研究进展
- Author:
Yang-yang CHEN
1
,
2
;
Ai-ying XIONG
3
;
Seng ZHU
3
;
Ge SONG
3
;
Hong TIAN
1
Author Information
1. School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
2. Shanghai Innovation Center, Shanghai Henlius Biotech, Inc., Shanghai 200233, China
3. Shanghai Innovation Center, Shanghai Henlius Biotech, Inc., Shanghai 200233, China
- Publication Type:Research Article
- Keywords:
conditional activation;
antibody;
pH;
adenosine triphosphate;
tumor-associated protease
- From:
Acta Pharmaceutica Sinica
2024;59(9):2429-2442
- CountryChina
- Language:Chinese
-
Abstract:
The high selectivity and affinity of antibody binding make antibodies widely used in therapeutics, diagnostics, and basic sciences. However, the toxicity of some antibodies has limited their utility. In the past decade, by increasing tissue specificity, conditionally active antibodies have further improved the safety and efficacy of antibodies, widened or even created a therapeutic window. Conditionally active antibodies are antibodies activatable under particular stimuli but have little or no antigen-binding activity in circulation and normal tissues. Conditionally active antibodies are designed to respond to endogenous or exogenous stimuli, such as light, temperature, enzymatic activity, pH, adenosine triphosphate (ATP), ions, effector molecules, and antigen combinations. Currently, two pH-activated antibodies have been approved for clinical use, and multiple conditionally active antibodies have entered clinical trials. This article describes the current status of the field of conditionally active antibodies, focusing on the three major types of conditionally active antibodies activated by pH, ATP and protease, including their design principles, implementation methods, relevant examples and the latest research progress. In addition, this review summarizes tumor-associated proteases and discusses the role of several key proteases in the development and progression of cancer, which can provide reference for the research and development of conditionally active antibodies. Many opportunities remain untapped in this field, waiting for more efficient and generally applicable activation strategies to be developed at the interface between chemistry and biotechnology.
