ICE Bioscience Posters

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Antibody-drug conjugates (ADCs) represent a promising antineoplastic strategy by combining antibody targeting with potent cytotoxic drugs. However, clinical challenges remain, including tumor non-responsiveness, drug resistance, and disease relapse, largely due to tumor heterogeneity and resistance mechanisms. Dual-payload ADCs have emerged as an innovative approach to improve efficacy through synergistic cytotoxicity, overcome resistance, and support flexible dosing regimens. The development of such ADCs relies on identifying effective payload combinations, which can be efficiently explored using cell panel screening and drug-resistant cell models. In this study, we performed large-scale combination screening in ADC-resistant cell lines to identify synergistic payload pairs. The screening panel included more than 120 targeted agents and chemotherapeutics. Our results identified that ATR inhibitors as well as CHK1/2 inhibitors exhibited favorable synergistic effects in combination with Topoisomerase I (TOPO1) inhibitors, whose detailed mechanisms warrant further validation. This optimized combination serves as a direct candidate for dual-payload ADC development, with the potential to accelerate the discovery and translation of next-generation ADC therapies.