Abstract 5279: The first ACT: an efficient data tracking and sharing tool for ADC and linker-payload development
Authors: Frank Loganzo, Ellie Muszynska, Nathan Tumey, Megan Tran, Tianhong Zhang
Journal: Cancer Research (2016)

Abstract Antibody drug conjugates (ADCs) are anti-cancer agents that more selectively deliver potent cytotoxins to tumors via targeted antigens. ADCs are modular biotherapeutics composed of antibody (Ab), linker (L), and payload (P). The LP may be conjugated to different antibody locations, including endogenous cysteine or lysine residues; recent advances in conjugation technology also have enabled site-specific conjugation to engineered cysteine, glutamine, or other sites. Pfizer has utilized a platform approach to identify novel LPs and ADCs, hence large numbers of linkers and payloads have been synthesized and conjugated to many different antibodies at conventional and site-specific locations. This has generated thousands of permutations of antibody, conjugation site, linker, and payload. Moreover, there are large volumes of metadata and analytical data associated with each ADC component as well as with the final conjugated product. Hence, there is an avalanche of data that must be tracked and accessed in order to ensure efficient decision making and communication as ADCs advance through our biological testing funnel. To handle this information challenge, we designed and implemented a new ADC tracking system. First, we created a systematic nomenclature to enable automated assignment of ADC names. ADC names are concatenated in the format “Ab-(site)_L_P”. In addition, specific antibody properties are defined within the Ab portion of the name, such as antigen, clone ID, mutation, isotype, etc. Second, we built a Java web-start enabled desktop application known as Antibody Conjugate Tracker (ACT). ACT integrates ADC bioanalytical and structural information into a user-friendly interface. The application recapitulates our synthesis and testing workflow: antibody inventory, LP inventory, project team synthesis requests, ADC registration, and sample physical inventory. ACT enables system-generated ADC name assignment by defined rules as well as registration of every ADC with corporate identifiers to allow biological data reporting. The systematic naming allows for facile uniqueness checking, thus eliminating possible redundancies and minimizing confusion about ADCs that use similar components. Third, we integrated ACT with the corporate registration system and the biological results database, allowing seamless access of in vitro and in vivo screening data for each ADC. By tracking both platform and program ADCs via ACT, we now have a rich database of constructs and biological results that can be used to interrogate structure-activity relationships (SAR) of new linker-payloads. Overall, benefits of the ACT system include more efficient conjugation workflows, inventory tracking, enhanced communication among scientists from synthesis to testing, and streamlined SAR analysis of novel linker-payloads. These efficiencies have ensured accurate tracking and delivery of innovative ADCs into our clinical development pipeline. Citation Format: Frank Loganzo, Ellie Muszynska, Nathan Tumey, Megan Tran, Tianhong Zhang. The first ACT: an efficient data tracking and sharing tool for ADC and linker-payload development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5279.