Abstract 4445: Diverse ADC novel payloads, comprehensive screening and evaluation platform

Abstract By combining the potency of payload with the specificity of antibody, Antibody-drug conjugate (ADC) is an innovative and promising drug modality for cancer therapy, possessing the advantages of both chemotherapy and immunotherapy. As ADC technology development continues to advance, more novel types of payloads are being actively explored.ICE Bioscience employed different screening approaches including biochemical, biophysical, cell-based, and LC/MS-based assays for payload screening and evaluation. To be specific, the methods for cytotoxic drug evaluations include microtubule polymerization assay, NMT1/2 FI assay, different biochemical assays for DNA-damage response (DDR) targets, and DNA topoisomerase inhibition assay; For degrader payloads, spectral shifts or HTRF can be applied for measuring binary/ternary complex formation, HiBiT system and WB assay for quantifying target degradation; For STING agonist/antagonist payload, ICE has ready-to-use assays for detecting STING binding, STING activation and cytokine release. Cell panels of different types of cancer cell lines, ADC-related drug-resistant cell lines, immunogenic cell death (ICD) evaluation, in vitro hematotoxicity prediction, as well as ADME evaluation especially permeability and lysosome stability assays are valuable for all different types of payloads.Based on 15 years of experience in early drug discovery, from target validation to pre-clinical candidate identification, our well-established ADC integrated platform can support comprehensive payload screening and evaluation early-stage drug discovery projects of traditional ADCs and emerging new ADC formats, including different cytotoxic payloads, novel degrader payloads and immune-related payloads, which can greatly accelerate ADC early-stage research. Citation Format: Ying Meng, Qian Wang, Min Kang, Xuan Qiao, Chanrui Wang, Yixiao Zhao, Jiangtao Lin, Jiamei Zhao, Li Li, Tiejun Bing. Diverse ADC novel payloads, comprehensive screening and evaluation platform abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4445.