Abstract 523: Advanced engineering using CAR-T display libraries: Ultra-high throughput functional screen

Abstract

CAR-T-cell therapies represent a new area of synthetic biology success in cancer immunotherapy. However, the complexity of their adverse events related to their activity are still a major challenge. Using our in-house fully human computationally optimized phage display library, we established a novel cell-based ultra-high throughput panning and screening CAR-T platform. Our proprietary CAR-T vector is designed as a series of cassettes incorporating our SuperHuman phage library with an optimal backbone. This allows us to design CAR-T with desired properties, including: Range of Affinities, Humanness, Epitope Diversity, Thermostability, Immunogenicity, Tonic activation, Toxicity, and Functional Activity. Our library's encoding ensures a single CAR-T construct per one reporter cell. Moreover, to confirm CAR-T-specific-activation, we incorporated three different markers that will be upregulated simultaneously. We used CD19 and BCMA to validate our platform selecting target-specific functionally active scFv candidates against both targets, which are selective to activation conditions such as tonic signaling, and tissue specific silencing. Collectively we show that our platform can be readily used to characterize CAR-T in high-speed and - throughput fashion. Citation Format: Sawsan Youssef, Joyce Chou, Devin Pineda, Sarah Ives, Valerie Chiou, Jean-Philippe Buerckert, Raymond Newland, Shahrad Daraeikia, Sindy Liao, Chelsea Jones, Christina Pettus, Jessica Salas, Emelia Padilla, Christopher Smith, Giles Day, David Maurer, Ian Waddell, Jacob Glanville. Advanced engineering using CAR-T display libraries: Ultra-high throughput functional screen [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 523.