Dissecting the tumour immune microenvironment and CAR-T cell therapy resistance - Dr. Maxine Lam

Glioblastoma (GBM) remains one of the most lethal malignancies with limited treatment options and dismal prognoses. Immunotherapy, particularly chimeric antigen receptor (CAR) T cell therapy, has emerged as a promising avenue for GBM treatment. However, the complex tumour immune microenvironment and the presence of the blood-brain barrier (BBB) present formidable challenges to the efficacy of CAR-T cell therapies. We present a novel in vitro model of GBM that incorporates a functional BBB, aiming to replicate the physiological barriers encountered by CAR-T cells in GBM patients. Utilizing this model, we investigated the efficacy of CAR-T therapy against GBM and identified a subset of GBM cells resistant to CAR-T treatment. By employing single-cell analyses, we delineated the dynamic changes occurring within the various cell types in the tumour microenvironment. We identify alterations in cell states in T cell phenotypes, GBM cell populations and the BBB after CAR-T therapy. Our findings shed light on the complexities underlying CAR-T immunotherapy for GBM and highlight the importance of developing strategies to overcome resistance mechanisms within the tumour microenvironment. This physiologically relevant model provides a valuable platform for preclinical testing and the optimization of CAR-T cell therapies, by enabling accurate and highly controlled in vitro experiments. Ultimately this will bring us closer to improved treatment strategies for this devastating disease.
Dr Maxine Lam earned her doctorate in Developmental and Stem Cell Biology from the MRC LMCB in London as a Wellcome Trust and A*STAR PhD fellow. Transitioning to cancer biology, she briefly worked at the Institute of Cancer Research before joining IMCB in 2020. Dr Lam received the Career Development Fund by A*STAR to develop an in vitro microphysiological model for glioblastoma and the blood-brain barrier. Collaborating across disciplines, she employs interdisciplinary approaches to unravel the complexities of brain cancers and advance novel perspectives in the field.
This webinar is co-organized by Singleron, Azenta, and RSC, A*STAR