Abstract C004: ADC screening platform, a useful platform for ADC drug evaluation

Abstract Since the approval of the first antibody-drug conjugate (ADC), Mylotarg, in 2000, the field has expanded significantly, with 15 currently approved ADCs and more than 210 in clinical development. ADC drug development has now reached a vibrant phase, demonstrating notable efficacy and favorable safety profiles against key targets such as HER2, EGFR, Trop2, CLDN18.2, and Nectin-4. The therapeutic potential of ADCs in oncology is vast and promising. ADCs are composed of three essential components: a monoclonal antibody, a linker, and a cytotoxic payload. The toxin, or payload, serves as a critical determinant of the drug’s potency. Approved ADC payloads are highly potent, including agents such as MMAE/MMAF, calicheamicin, DM1/DM4, SN38/Dxd, among others. These compounds exhibit toxicity levels up to 1–2 orders of magnitude greater than conventional chemotherapeutics, with some operating at pM concentrations. Emerging payloads under investigation employ diverse mechanisms, such as DNA alkylating agents, topoisomerase inhibitors, microtubule destabilizers, and RNA polymerase II inhibitors. We have compiled an extensive cell bank comprising over 800 human tumor cell lines and 100 animal-derived tumor cell lines, representing a wide spectrum of cancer types. Leveraging this comprehensive resource, we are developing an ADC screening platform. Through systematic testing, we generate efficacy data across various cell lines and payloads, enabling informed selection of appropriate models for in vitro ADC evaluation. To date, we have evaluated over 200 frequently used cell lines—predominantly breast cancer lines—using multiple payloads, including MMAE, SN38, Dxd, and exatecan. Our goal is to complete testing on all available cell lines within one year. This ADC screening platform represents a large-scale initiative that will significantly enhance our ability to screen and evaluate ADC candidates efficiently and effectively. Citation Format: JINYING B. NING, Feng B. Hao, Thomas B. Strong. ADC screening platform, a useful platform for ADC drug evaluation [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C004.