1119 Pool discovery of chimeric antigen receptors to program macrophages
Year: 2024
Type: conference-abstract
Abstract: Background Chimeric antigen receptors (CARs) have been primarily designed based on endogenous T-cell molecules, such as CD3 and CD8, for over 35 years. However, the suitability of T-cell-based CAR structures for other immune cell types remains unclear. Notably, CD28 and 4-1BB CARs, which perform well in T-cells, exhibit compromised protein trafficking in macrophages. This prompted us to explore optimal CAR structures for macrophages. Methods We conducted a pooled library screening of CAR structures incorporating macrophage-specific endogenous signal peptides, hinge regions, transmembrane, and signaling domains.1 Using a modular cloning strategy, we generated a library of 50,000 CAR variants for functional screening. Our FlowSeq approach enables the identification of CARs that enhance phagocytosis and cytotoxic cytokine secretion. Results and Conclusions To further refine our findings, we employed neural networks to infer a larger library and define the most effective CAR structures for macrophages. This high-throughput strategy, combined with advanced neural network analysis, paves the way for the discovery of novel CARs tailored for immunotherapy. Acknowledgements This research is supported by Health@InnoHK, the Innovation and Technology Commission of the Government of HKSAR. Reference Ronan W O’Connell, Caleb J Bashor. Ultra-high throughput mapping of genetic design space. bioRxiv[Preprint]. 2023 Jul 6:2023.03.16.532704.
Authors: Lu Liu, Sophronia Yip, Shi hui Zhang, Theo Aurich, Rio Sugimura
Institutions: Heidelberg University, University of Hong Kong
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4404065255