Antibody-drug conjugates (ADCs) are primarily composed of three “modules”: an antibody (usually a monoclonal antibody), a linker, and a cytotoxic drug (payload). In recent years, ADCs have stood out among biological drugs due to their combination of the potent killing effect of chemotherapy agents and the precise targeting of antibody drugs, earning the title of “biological missiles” and becoming a hotspot in cancer treatment research, gradually expanding their range of indications. For these long-term use drugs, they significantly reduce side effects based on traditional chemotherapy methods, increase medication safety, and enhance patient compliance.
Diagram of ADC drug structure
As of August 2022, five ADCs have been approved for marketing in China: Emicizumab (brand name: Herceptin, T-DM1), Vabomere (brand name: Anshili), Vadastuximab (brand name: Aidiqi), Ogivri (brand name: Beibosa), and Gemtuzumab (brand name: Tuodavi). Additionally, there are over 100 ADC candidates in clinical stages globally, with numbers continuing to rise.
With the in-depth development of ADCs, the first generation of cleavable linkers connected to mouse or chimeric antibodies has evolved into second-generation fully humanized antibodies, further developing into site-specific conjugates of fully human antibodies or Fab fragments. This has led to the development of three generations of ADC products, further improving the stability of ADC drug molecules, making the drug-antibody conjugation ratio (DAR) more controllable, reducing immunogenicity, and enhancing drug safety and efficacy.
Summary of the characteristics of three generations of ADC products
(Data source: Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduction and Targeted Therapy (2022) 7:93)
To ensure drug safety, efficacy, and quality control, research on its critical quality attributes is essential. Compared to standalone antibody molecules or cytotoxic drugs, ADCs have a more complex molecular structure, and the large antibody molecules must maintain their biological activity. Size exclusion chromatography (SEC) is commonly used to detect aggregates and fragment impurities, while ion exchange chromatography (IEX) is used for studying critical quality attributes and charge heterogeneity. The purity of small molecule compounds is a key quality attribute, with reversed-phase chromatography being the most commonly used detection method. Additionally, for both natural and synthetic cytotoxic molecules, chirality should also be examined. The DAR of ADCs after conjugation is a key indicator determining the drug’s effective payload, with hydrophobic interaction chromatography (HIC) being the current standard detection method. Furthermore, small-pore SEC chromatography is often used in stability studies to detect small molecule leakage. Therefore, for ADCs, corresponding analytical methods need to be developed for different “modules,” bringing greater challenges to their quality research.
Saifen Technology has rich experience in developing analytical methods for ADC drugs, with certain technical accumulation in antibody molecule analysis, ADC drug purity analysis, and DAR value detection.
Here, on November 8th from 1:30 PM to 2:30 PM, Saifen Technology will hold an online exchange meeting on “Development of Analytical Methods for ADC Drugs” in collaboration with the Bioproduct Circle, and we look forward to your participation.
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【Speaker Introduction】
Wang Shuai
Director of Analytical Chromatography Technology at Suzhou Saifen Technology Co., Ltd.
Wang Shuai, graduated from Shanghai Ocean University with a master’s degree in Food Engineering, currently serves as the Director of Analytical Chromatography Technology at Suzhou Saifen Technology. Previously, he worked as a training engineer for Thermo Fisher’s liquid chromatography product line. After joining Saifen Technology, he has been responsible for the development of analytical methods for biomedicine, organizing and participating in technical support for over 1000 different biological sample projects, and has accumulated rich experience in developing analytical methods for antibodies, ADCs, mRNA, and other biological macromolecules.
About Saifen Technology Saifen Technology was founded in Delaware, USA, and has focused on chromatography technology for nearly 20 years, serving over 5000 global customers.
Saifen Technology focuses on biological macromolecules such as antibodies, vaccines, insulin, recombinant proteins, and mRNA, providing full-cycle analytical chromatography and industrial purification solutions for Chinese biopharmaceutical companies based on top international R&D capabilities and a production base in Yangzhou that produces 100,000 liters of chromatography media annually.
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