Over 800! Establishment of an ADC payload efficacy database across diverse tumor cell lines: Foundation for optimized in vitro ADC evaluation and drug development

Ever since the first antibody-drug conjugate (ADC), Mylotarg, received approval back in 2000, the ADC market has expanded to include 15 approved products so far, while more than 210 others are currently in clinical trials. This indicates that ADC drug development has stepped into a thriving phase-especially when targeting molecules like HER2, EGFR, Trop2, CLDN18.2, and Nectin-4, ADCs have demonstrated notable efficacy and favorable safety profiles. As such, ADC therapy holds extremely broad application prospects in the field of cancer treatment.Antibody-drug conjugates (ADCs) consist of three core components: a monoclonal antibody, a linker, and a toxin. Among these, the ADC toxin-also referred to as the ADC payload-is a critical element of ADC drugs, as it serves as the key factor determining the drug's potency. The payloads used in approved ADCs are highly toxic; major examples include MMAE/MMAF, calicheamicin, DM1/DM4, and SN38/Dxd. Compared with traditional chemotherapy drugs, these payloads are 1 to 2 orders of magnitude more toxic, and some even reach toxicity levels in the picomolar (pM) range. For payloads currently under development, their mechanisms of action mainly fall into four categories: DNA alkylating agents, DNA topoisomerase inhibitors, microtubule disruptors, and RNApolII inhibitors.We have established an extensive cell bank, which houses over 800 human tumor cell lines and 100 animal tumor cell lines, covering all types of cancers. Leveraging this rich cell resource, we are constructing an ADC screening platform. Through comprehensive testing, we collect efficacy data of different ADC payloads across various cell lines-this data then guides us in selecting appropriate cell lines for in vitro ADC evaluation. Up to now, we have already finished over 700 commonly used cell lines using several ADC payloads, such as MMAE, SN38, Dxd, and exatecan. As a large-scale initiative, the ADC screening platform is expected to play a positive and supportive role in the screening and evaluation of ADC drugs.