#Immunotherapy #TCells #CancerResearch #BiomedicalEngineering #OpenAccess #NatureBiomedicalEngineering

The work was led by our talented student Jose Cabezas Caballero (now a postdoc with Mala Maini) and huge thanks to all the co-authors and collaborators who made this work possible, and to Springer Nature Biomedical Engineering for an efficient review process.

This approach offers a universal method to generate highly selective therapeutic T cells for any TCR, potentially improving both the safety and effectiveness of adoptive immunotherapy for a wide range of targets.

Our work shows that by modulating co-signalling receptors on T cells (such as switching CD8 for CD4), we can significantly and selectively reduce lower-affinity off-target activation while keeping higher-affinity antitumor target efficacy intact.

In this study, we explore a novel strategy to enhance the safety of T cell immunotherapies. Traditional engineered T cell receptors (TCR-T) can sometimes cross-react with unintended lower-affinity targets, leading to harmful side effects.

The work was lead by Anna H. with support from many lab members, a fantastic collaboration with Audrey Gerard with support from Wellcome Trust and BBSRC. Thank you to EMBO Journal for a constructive and efficient review process.

We suggest that T cells 'force-shield' their TCR/pMHC interactions at interfaces to faithfully measure their affinities.

We show that despite the enormous molecular complexity at T cell interfaces (with target cells), the 3D affinity measured with purified TCR and pMHC in SPR can accurately predict the OT-I T cell response.

With a News & Views by Pierre Bongrand and Philippe Robert
Unraveling T-cell decoding strategy: a step forward
www.embopress.org/doi/full/10....

Thanks to our funding, collaborators, constructive reviewers, and for the very efficient process at Immunology & Cell Biology!

By comparing the advantages and limitations of each platform, we provide a framework to choose the most suitable system to study signal integration in both basic and translational contexts.

A recently developed CombiCell system enables easy manipulation of ligands while conserving key biophysical properties.

In contrast, solid surfaces or supported lipid bilayers allow easy manipulation of ligands but lack the biophysical properties of cells, such as softness, a glycocalyx, and/or ligand mobility.

Although genetically modified antigen-presenting cells (APCs) offer the most physiological system, manipulating their ligands is difficult and slow.

We review and compare the available platforms, focusing on T-cell recognition.