(Solving T-cell receptor recognition and design via integrated high-throughput screening and structural, functional and computational approaches)

CHALLENGE: T-cell receptors
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Team MATCHMAKERS aims to take an integrated approach to understand how T cells recognise tumours, to pave the way for personalised immunotherapies.  

Team Lead
Michael Birnbaum (Massachusetts Institute of Technology)
Germany, Netherlands, Norway, US

The idea

Understanding how T-cell receptors (TCRs) see tumour antigens presented by protein complexes on the surface of cancer cells (called major histocompatibility complexes or MHCs) is necessary to fully understand how the immune system recognises cancer.  

MATCHMAKERS’ overarching goal is to predict what T cells recognise in individual tumours using simple laboratory tests and computational prediction. To make this goal a reality, the team hopes to develop novel methods and new algorithms, and create large, integrated datasets of TCRs and peptide-MHCs.  

The team aims to develop and implement approaches that can capture the TCR and antigen repertoire diversity that is inherent to the function of the immune system, build systems for antigen-specific TCR evolution, match TCRs to their cognate antigens, perform large-scale structural characterisations of TCR-peptide-MHC complexes and develop computational models.  

Uniting world leaders in cancer immunology, genetics, high throughput method development, structural biology and computer science, the team hopes to ultimately use its approaches to generate tumour antigen-specific TCRs for use in personalised immunotherapies. 

"Each of the challenges addresses compelling questions in cancer research, and the talent being brought to bear to address them is immense. Our team believes that the collaborative work that could be enabled by this grant will directly translate to impact for people with cancer."