整合式ADC平台：从发现到功能评价

Antibody-Drug Conjugates (ADCs) represent a rapidly advancing modality with elegantly simple and compelling mechanisms. They have proven successful not only in combating cancer but have also recently expanded into other therapeutic areas such as autoimmune diseases. Despite these advancements, challenges such as new payload exploration, antibody penetration, increasing ADC uptake and processing, and overcoming ADC resistance continue to persist. Our comprehensive antibody discovery platform excels in generating high-affinity antibodies against challenging antigens, particularly multi-pass transmembrane proteins. By combining this with advanced high-throughput screening capabilities, we efficiently identify potent antibody candidates, thereby accelerating the antibody discovery process. To further expedite ADC discovery with high efficiency, we have developed a state-of-the-art high-throughput conjugation platform integrated with various downstream biological assays. Utilizing parallel synthesis and analytics, we can generate and evaluate ADCs with diverse linkers and payloads at microgram to milligram scales within 2-3 weeks. IgG1 antibodies are used, and products are isolated through resin purification. These ADCs exhibit uniform Drug-to-Antibody Ratios (DAR), consistent analytical size-exclusion chromatography (aSEC) profiles, and precise concentration ranges, with less than 0.1% free drug residue. This facilitates the simultaneous construction of hundreds of conjugate variants per run, allowing for rapid cytotoxicity and stability assays to triage and prioritize candidates for further development. In addition to high-throughput antibody screening and conjugation, our well-established full-spectrum ADC platform provides comprehensive services from payload assessment and ADC in vitro efficacy evaluation to supporting in-depth mechanistic exploration. This includes studying antibody internalization, killing effects, bystander evaluation and the development of potential resistance. Through continuous expansion of this platform, we are not only enabling early-stage ADC drug discovery but also addressing emerging challenges in the field.