Patients with gastrointestinal irritability after TGN1412-induced cytokine storm displayed selective expansion of gut-homing αβ and γδT cells.

Autor: McCarthy NE; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK. n.e.mccarthy@qmul.ac.uk.; Centre for Immunobiology, The Blizard Institute, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. n.e.mccarthy@qmul.ac.uk., Stagg AJ; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK.; Centre for Immunobiology, The Blizard Institute, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Price CL; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK.; Lucid Group Communications, Buckinghamshire, UK., Mann ER; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK.; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK., Gellatly NL; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK., Al-Hassi HO; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK.; Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK., Knight SC; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK., Panoskaltsis N; Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, London, UK. nicki.panoskaltsis@emory.edu.; Department of Haematology, Imperial College London, Northwick Park and St. Mark's Campus, London, UK. nicki.panoskaltsis@emory.edu.; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA. nicki.panoskaltsis@emory.edu.; BioMedical Systems Engineering Laboratory, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA. nicki.panoskaltsis@emory.edu.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2021 Apr; Vol. 70 (4), pp. 1143-1153. Date of Electronic Publication: 2020 Oct 13.
DOI: 10.1007/s00262-020-02723-4
Abstrakt: Following infusion of the anti-CD28 superagonist monoclonal antibody TGN1412, three of six previously healthy, young male recipients developed gastrointestinal irritability associated with increased expression of 'gut-homing' integrin β7 on peripheral blood αβT cells. This subset of patients with intestinal symptoms also displayed a striking and persistent expansion of putative Vδ2 + γδT cells in the circulation which declined over a 2-year period following drug infusion, concordant with subsiding gut symptoms. These data demonstrate that TGN1412-induced gastrointestinal symptoms were associated with dysregulation of the 'gut-homing' pool of blood αβ and γδT cells, induced directly by the antibody and/or arising from the subsequent cytokine storm.
Databáze: MEDLINE
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