Abstract 6843: MegaScreen, a useful platform for ADC drug evaluation

Abstract Since the approval of the first antibody-drug conjugate (ADC) , Mylotarg, in 2000, there are now 15 approved ADCs on the market, with over 210 in clinical trials. The development of ADC drugs has entered a flourishing stage, particularly showing significant efficacy and good safety in targets such as HER2, EGFR, Trop2, CLDN18.2, and Nectin-4. The application prospects of ADC therapy in cancer treatment are very broad. ADCs are drugs composed of three parts: a monoclonal antibody, a linker, and a toxin. Among these, the ADC toxin, also known as the ADC payload, is a crucial component of ADC drugs. The toxin is the key to determining the potency of the ADC drug. The payloads of approved ADC drugs are highly toxic, primarily including MMAE/MMAF, calicheamicin, DM1/DM4, SN38/Dxd, etc. These payloads are 1-2 orders of magnitude more toxic than chemotherapy drugs, with some even reaching pM levels. The mechanisms of action of the payloads currently under development mainly include DNA alkylating agents, DNA topoisomerase inhibitors, microtubule disruptors, and RNApolII inhibitors. We have established a substantial cell bank, containing over 800 human tumor cell lines and 100 animal tumor cell lines, covering all types of cancers. Based on this rich cell bank, we are building an Megascreen platform. Through extensive testing, we obtain efficacy data for different ADC payloads across various cell lines, guiding us in selecting suitable cell lines for in vitro evaluation of ADCs. To date, we have tested more than 200 commonly used cell lines particularly breast cancer cell lines. with several ADC palyloads, such as MMAE, SN38, Dxd, exatecan. Our plan is to complete testing of all cells within a year. This Megascreen platform is a large-scale project that will significantly contribute to the screening and evaluation of ADCs. Citation Format: Guoqian Wang, Yao Tang, Jingxiao Xu, Tingduo Lv, Jinying Ning, Feng Hao. MegaScreen, a useful platform for ADC drug evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6843.