Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes

Professor Omer Dusk discusses a bioRxiv pre-print: ‘Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes’. This episode discusses the following pre-print: 'Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes.' Burton J, Siller-Farfan JA, Andre V, Jenkins J, Barton MI, Bustamante Eguiguren S, Cabezas-Caballero J, Davis SJ, Weikl TR, van der Merwe PA, Dushek O (bioRxiv pre-print (2025), under review). https://www.biorxiv.org/content/10.1101/2025.01.06.631424v1 And references two related studies that provide foundational framework for the work: Using CombiCells, a platform enabling titration and combinatorial display of cell surface ligands, to study T cell antigen sensitivity by TCRs, CARs, and BiTEs Patel A, Andre V, Eguiguren SB, Barton MI, Denham EM, Pettmann J, Morch AM, Kutuzov MA, Siller-Farfan JA, Dustin ML, van der Merwe PA, Dushek O The EMBO Journal (2024) https://www.biorxiv.org/content/10.1101/2023.06.15.545075v2 Inefficient exploitation of accessory receptors reduces the sensitivity of chimeric antigen receptors Burton J, Siller-Farfan JA, Pettmann J, Salzer B, Kutuzov M, van der Merwe PA, Dushek O PNAS (2023). https://www.pnas.org/doi/abs/10.1073/pnas.2216352120 A full list of contributors and acknowledgements can be found within each article. Additionally, Professor Omer Dushek would like to thank past and present members of his laboratory, including all co-authors of the manuscript, and especially his long-term collaborator P. Anton van der Merwe (co-founder). The establishment of MatchBio Ltd relied on technology to improve the sensitivity of CAR-T cells and technology to manipulate surface proteins directly on the cell surface (CombiCells) that included critical contributions from Jake Burton, Jesús Siller-Farfan, Violaine Andre, Michael I. Barton, Ashna Patel, Eleanor Denham, Edward Jenkins, Simon J. Davis, Sofia Bustamante Eguiguren, Jose Cabezas Caballero, Thomas R Weikl, and Johannes Pettmann. The founding of MatchBio Ltd relied on the expertise of Philip G. Jakeman (CEO) and the OSE Life Science Panel. The work has been supported by the Wellcome Trust (207537/Z/17/Z) and UKRI MRC (MR/W031353/1). Speakers: Professor Omer Dushek, Professor Paul Klenerman