Caroline Lamarche1, Megan K Levings. 1. Department of Surgery, University of British Columbia & British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
Abstract
PURPOSE OF REVIEW: The application of regulatory T cell (Treg) therapy in organ transplantation is actively being pursued using unmodified, typically polyclonal cells. As the results of these ongoing clinical trials emerge, it is time to plan the next wave of clinical trials of Tregs. Here we will review a key strategy to improve Treg effectiveness and reduce side effects, namely increasing Treg specificity - both in terms of antigen recognition and localization to the allograft. RECENT FINDINGS: Study of chemokine signatures accompanying acute rejection has revealed several chemokines that could be targeted to increase Treg homing. For example, Tregs possessing a Th1-like phenotype and expressing CXCR3 are better able to migrate towards local inflammation. Allografts themselves can be modified to increase Treg-attracting chemokines and Tregs themselves can produce chemokines, facilitating local proximity to their targets of suppression. Finally, tailoring Treg antigen specificity by T-cell or chimeric antigen receptor engineering is another approach to increase the specificity of suppression and optimize localization. SUMMARY: Treg localization to the graft is important, but the important role of lymph node and germinal center homing cannot be overlooked. There is an opportunity to learn from advances made in cancer immunotherapy to optimize Treg therapy for transplantation.
PURPOSE OF REVIEW: The application of regulatory T cell (Treg) therapy in organ transplantation is actively being pursued using unmodified, typically polyclonal cells. As the results of these ongoing clinical trials emerge, it is time to plan the next wave of clinical trials of Tregs. Here we will review a key strategy to improve Treg effectiveness and reduce side effects, namely increasing Treg specificity - both in terms of antigen recognition and localization to the allograft. RECENT FINDINGS: Study of chemokine signatures accompanying acute rejection has revealed several chemokines that could be targeted to increase Treg homing. For example, Tregs possessing a Th1-like phenotype and expressing CXCR3 are better able to migrate towards local inflammation. Allografts themselves can be modified to increase Treg-attracting chemokines and Tregs themselves can produce chemokines, facilitating local proximity to their targets of suppression. Finally, tailoring Treg antigen specificity by T-cell or chimeric antigen receptor engineering is another approach to increase the specificity of suppression and optimize localization. SUMMARY: Treg localization to the graft is important, but the important role of lymph node and germinal center homing cannot be overlooked. There is an opportunity to learn from advances made in cancer immunotherapy to optimize Treg therapy for transplantation.
Authors: Nicholas Aj Dawson; Caroline Lamarche; Romy E Hoeppli; Peter Bergqvist; Vivian Cw Fung; Emma McIver; Qing Huang; Jana Gillies; Madeleine Speck; Paul C Orban; Jonathan W Bush; Majid Mojibian; Megan K Levings Journal: JCI Insight Date: 2019-03-21
Authors: Mohamed B Ezzelarab; Hong Zhang; Kazuki Sasaki; Lien Lu; Alan F Zahorchak; Dirk J van der Windt; Helong Dai; Angelica Perez-Gutierrez; Jay K Bhama; Angus W Thomson Journal: Transplantation Date: 2021-09-01 Impact factor: 5.385