A5008701517- CAR-T cell therapy research
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
University of Oxford
2020-2023
Science Oxford
2023
John Radcliffe Hospital
2020-2023
Medical Research Council
2021
MRC Human Immunology Unit
2020
Abstract T cells use finger-like protrusions called ‘microvilli’ to interrogate their targets, but why they do so is unknown. To form contacts, must overcome the highly charged, barrier-like layer of large molecules forming a target cell’s glycocalyx. Here, are observed microvilli breach model glycocalyx barrier, numerous small (<0.5 μm diameter) contacts each which stabilized by adhesive protein CD2 expressed cell, and excludes proteins including CD45, allowing sensitive, antigen...
Significance Microvilli are used by immune cells to sense the surface features of pathogens and antigen presenting cells. However, microvilli’s contribution in T cell signaling activation is largely unknown. Here, we introduce a material-based platform for induction microvilli formation cells, which dimensions can be controlled tuning nanotopographical features, such as pore depth, size, interpore distance. We demonstrate direct causality between altered gene expression discover that size...
Abstract Adoptive cell therapy is becoming a cornerstone of tumour immunotherapy. It relies on the relatively long-term (> 2 week) ex vivo expansion T cells either in form tumour-infiltrating cells, or bulk modified with expression heterologous signalling proteins, e.g., chimeric antigen receptors. However, little known about developmental trajectories under these conditions at system level, whether pathways governing could be manipulated for clinical advantage. Using RNA-seq analysis...
The recent success of immunotherapies relying on manipulation T-cell activation highlights the value characterising mediators immune checkpoint signaling. CRISPR/Cas9 is a popular approach for interrogating signaling pathways; however, lack appropriate assays studying inhibitory in T cells limiting use large-scale perturbation-based approaches. Here, we adapted an existing Jurkat cell-based transcriptional reporter assay to study both activatory and (PD-1-mediated) using CRISPR-based genome...