Faculty

Laurie Menger is an INSERM immuno-biotechnologist. She is the group leader of the Advanced T-cell therapy team (ATIP-2022, U1015) at Gustave Roussy, the leading cancer center in Europe. She benefits from long expertise in high throughput screening strategies (Sci Transl Med 2012, patent WO2010EP55404), T cell therapy and engineering from UCL Cancer Institute and Institut Curie. She previously established clinically relevant protocols to KO immunosuppressive genes such as the glucocorticoid receptor in viral-specific T cells (Blood 2015). She was also the first to inactivate PD1 in tumor-infiltrating lymphocytes (Cancer Res 2016) to strengthen T-cell therapies. She established genome-wide engineering of primary T-cells to accelerate target discovery (STAR protocol 2023). With this systematic interrogation, her team identified SOCS1 as a major checkpoint inhibitor of CD4 T cells, whose inactivation restored CAR19 T cells persistence, composition and efficacy in vivo (Sci Immunol 2021). Her team recently interrogated genes providing T cells with resistance to allogeneic rejection in vivo for the widespread translation of T-cell therapy as a drug. They identified Fas as a major target and demonstrated that base-edited CD3/FAS-KO human CAR-T cells outperform CD3/B2M-KO CAR-T in resistance to both allo-T and NK cells mediated rejection (Nat. Biomed Engin, 2024, patent WO2022023576A1). This discovery challenges the current dogma of deleting B2M and will pave the way for rapid/easy/safe production of allo-CAR-T from healthy donors. Her team was the first in Europe to establish in vivo genome-wide CRISPR screens in primary T cells, developing a functional pipeline to systematically characterize target genes reprogramming T-cell functionality in complex immunosuppressive intercellular interactions recapitulating patient’s tumor microenvironment. They are now integrating additional developments in synthetic biology using genome-scale CRISPR activation editing, deciphering the regulators of CD4 antitumor immune responses (EP24305178.6), developing translational models with base-edited expanded tumor-infiltrating lymphocytes, combinatorial CAR therapies and targeted delivery of chromatin modifiers providing resistance to exhaustion.