Fitxers

2023_57_Betriu_Rovira_HLA_A2-CHAR-Tc.pdf (3.66 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2023-10-01

Llicència de publicació

cc-by-nc (c) Betriu Méndez, Sergi et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224369

Chimeric HLA antibody receptor T cells for targeted therapy of antibody-mediated rejection in transplantation

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1111/tan.15156

Resum

The presence of donor-specific antibodies (DSA), mainly against HLA, increases the risk of allograft rejection. Moreover, antibody-mediated rejection (ABMR) remains an important barrier to optimal long-term outcomes after solid organ transplantation. The development of chimeric autoantibody receptor T lymphocytes has been postulated for targeted therapy of autoimmune diseases. We aimed to develop a targeted therapy for DSA desensitization and ABMR, generating T cells with a chimeric HLA antibody receptor (CHAR) that specifically eliminates DSA-producing B cells. We have genetically engineered an HLA-A2-specific CHAR (A2-CHAR) and transduced it into human T cells. Then, we have performed in vitro experiments such as cytokine measurement, effector cell activation, and cytotoxicity against anti-HLA-A2 antibody-expressing target cells. In addition, we have performed A2-CHAR-Tc cytotoxic assays in an immunodeficient mouse model. A2-CHAR expressing T cells could selectively eliminate HLA-A2 antibody-producing B cells in vitro. The cytotoxic capacity of A2-CHAR expressing T cells mainly depended on Granzyme B release. In the NSG mouse model, A2-CHAR-T cells could identify and eradicate HLA-A2 antibody-producing B cells even when those cells are localized in the bone marrow. This ability is effector:target ratio dependent. CHAR technology generates potent and functional human cytotoxic T cells to target alloreactive HLA class I antibody-producing B cells. Thus, we consider that CHAR technology may be used as a selective desensitization protocol or an ABMR therapy in transplantation.© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.

Matèries

Matèries (anglès)

Citació

Col·leccions

Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

BETRIU MÉNDEZ, Sergi, et al. Chimeric HLA antibody receptor T cells for targeted therapy of antibody-mediated rejection in transplantation. HLA. 2023. Vol. 102, num. 449-463. ISSN 2059-2310. [consulted: 28 of June of 2026]. Available at: https://hdl.handle.net/2445/224369

Exportar metadades

JSON - METS

Compartir registre