A conversation with Fadi Issa about his recent article on regulatory T cell therapy in kidney transplants. In this episode of To Immunity and Beyond, Paul Klenerman talks with surgeon and immunologist Fadi Issa about pioneering regulatory T-cell therapy in kidney transplantation. Fadi shares his journey from reconstructive surgery to immune tolerance research and discusses the groundbreaking, first-in-human ONE Trial of T reg therapy in kidney transplantation. The trial showed promising graft survival rates, and found B cell-enriched focal lymphocytic infiltrates in the T reg treated group. Paul and Fadi also explore how current work with spatial transcriptomics will enable further insights into this mechanism.
Full article: Oliver McCallion, Amy R. Cross, Matthew O. Brook, Conor Hennessy, Ricardo Ferreira, Dominik Trzupek, William R. Mulley, Sandeep Kumar, Maria Soares, Ian S. Roberts, Peter J. Friend, Giovanna Lombardi, Kathryn J. Wood, Paul N. Harden, Joanna Hester, Fadi Issa, Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants, Med, Volume 6, Issue 5, 2025, 100561, ISSN 2666-6340, https://doi.org/10.1016/j.medj.2024.11.014.
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A conversation with Fadi Issa about his recent article on regulatory T cell therapy in kidney transplants. In this episode of To Immunity and Beyond, Paul Klenerman talks with surgeon and immunologist Fadi Issa about pioneering regulatory T-cell therapy in kidney transplantation. Fadi shares his journey from reconstructive surgery to immune tolerance research and discusses the groundbreaking, first-in-human ONE Trial of T reg therapy in kidney transplantation. The trial showed promising graft survival rates, and found B cell-enriched focal lymphocytic infiltrates in the T reg treated group. Paul and Fadi also explore how current work with spatial transcriptomics will enable further insights into this mechanism.
Full article: Oliver McCallion, Amy R. Cross, Matthew O. Brook, Conor Hennessy, Ricardo Ferreira, Dominik Trzupek, William R. Mulley, Sandeep Kumar, Maria Soares, Ian S. Roberts, Peter J. Friend, Giovanna Lombardi, Kathryn J. Wood, Paul N. Harden, Joanna Hester, Fadi Issa, Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants, Med, Volume 6, Issue 5, 2025, 100561, ISSN 2666-6340, https://doi.org/10.1016/j.medj.2024.11.014.
Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes
To Immunity and Beyond
28 minutes
10 months ago
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 Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales; http://creativecommons.org/licenses/by-nc-sa/2.0/uk/
To Immunity and Beyond
A conversation with Fadi Issa about his recent article on regulatory T cell therapy in kidney transplants. In this episode of To Immunity and Beyond, Paul Klenerman talks with surgeon and immunologist Fadi Issa about pioneering regulatory T-cell therapy in kidney transplantation. Fadi shares his journey from reconstructive surgery to immune tolerance research and discusses the groundbreaking, first-in-human ONE Trial of T reg therapy in kidney transplantation. The trial showed promising graft survival rates, and found B cell-enriched focal lymphocytic infiltrates in the T reg treated group. Paul and Fadi also explore how current work with spatial transcriptomics will enable further insights into this mechanism.
Full article: Oliver McCallion, Amy R. Cross, Matthew O. Brook, Conor Hennessy, Ricardo Ferreira, Dominik Trzupek, William R. Mulley, Sandeep Kumar, Maria Soares, Ian S. Roberts, Peter J. Friend, Giovanna Lombardi, Kathryn J. Wood, Paul N. Harden, Joanna Hester, Fadi Issa, Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants, Med, Volume 6, Issue 5, 2025, 100561, ISSN 2666-6340, https://doi.org/10.1016/j.medj.2024.11.014.
