-
Tytuł:
-
In vitro elimination of autoreactive B cells from rheumatoid arthritis patients by universal chimeric antigen receptor T cells.
-
Autorzy:
-
Zhang B; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.; Clinical Immunology Center& Epigenetics Center, Peking Union Medical College Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing, China.
Wang Y; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Yuan Y; Clinical Immunology Center& Epigenetics Center, Peking Union Medical College Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing, China.
Sun J; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Liu L; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Huang D; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Hu J; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; Clinical Immunology Center& Epigenetics Center, Peking Union Medical College Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing, China.
Wang M; Clinical Immunology Center& Epigenetics Center, Peking Union Medical College Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing, China.; Department of Rheumatology & Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Li S; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Song W; Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chen H; Department of Rheumatology & Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zhou D; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China .
Zhang X; Clinical Immunology Center& Epigenetics Center, Peking Union Medical College Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing, China .; Department of Rheumatology & Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
-
Źródło:
-
Annals of the rheumatic diseases [Ann Rheum Dis] 2021 Feb; Vol. 80 (2), pp. 176-184. Date of Electronic Publication: 2020 Sep 30.
-
Typ publikacji:
-
Evaluation Study; Journal Article; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: London : BMJ
Original Publication: London : H.K. Lewis
-
MeSH Terms:
-
Arthritis, Rheumatoid/*therapy
Fluorescein-5-isothiocyanate/*therapeutic use
Immunotherapy, Adoptive/*methods
Receptors, Antigen, T-Cell/*therapeutic use
Receptors, Chimeric Antigen/*therapeutic use
Adult ; Antigen-Presenting Cells/immunology ; Arthritis, Rheumatoid/immunology ; Autoantigens/immunology ; B-Lymphocytes/immunology ; Collagen Type II/immunology ; Epitopes/immunology ; Female ; Fibrinogen/immunology ; Humans ; Ligands ; Male ; Peptides, Cyclic/immunology ; Proof of Concept Study ; Tenascin/immunology ; Vimentin/immunology
-
Contributed Indexing:
-
Keywords: anti-citrullinated protein antibodies; arthritis; autoimmune diseases; rheumatoid
-
Substance Nomenclature:
-
0 (Autoantigens)
0 (Collagen Type II)
0 (Epitopes)
0 (Ligands)
0 (Peptides, Cyclic)
0 (Receptors, Antigen, T-Cell)
0 (Receptors, Chimeric Antigen)
0 (Tenascin)
0 (Vimentin)
0 (cyclic citrullinated peptide)
9001-32-5 (Fibrinogen)
I223NX31W9 (Fluorescein-5-isothiocyanate)
-
Entry Date(s):
-
Date Created: 20201001 Date Completed: 20210217 Latest Revision: 20210217
-
Update Code:
-
20240105
-
DOI:
-
10.1136/annrheumdis-2020-217844
-
PMID:
-
32998865
-
Objectives: Autoreactive B cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA), and B cell-depleting therapies using an antibodies, such as rituximab, have been suggested to be effective in RA treatment. However, transient B cell depletion with rituximab is associated with significant safety challenges related to global suppression of the immune system and thus increases the risks of infection and cancer development. To address selective and persistent issues associated with RA therapy, we developed a customised therapeutic strategy employing universal antifluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) combined with FITC-labelled antigenic peptide epitopes to eliminate autoreactive B cell subsets recognising these antigens in RA.
Methods: For a proof-of-concept study, four citrullinated peptide epitopes derived from citrullinated autoantigens, namely, citrullinated vimentin, citrullinated type II collagen, citrullinated fibrinogen and tenascin-C, and a cyclocitrulline peptide-1 were selected as ligands for targeting autoreactive B cells; Engineered T cells expressing a fixed anti-FITC CAR were constructed and applied as a universal CAR-T cell system to specifically eliminate these protein-specific autoreactive B cells via recognition of the aforementioned FITC-labelled autoantigenic peptide epitopes.
Results: We demonstrated that anti-FITC CAR-T cells could be specifically redirected and kill hybridoma cells generated by immunisation with antigenic peptides, and autoreactive B cell subsets from RA patients via recognition of corresponding FITC-labelled citrullinated peptide epitopes. Additionally, the cytotoxicity of the CAR-T cells was dependent on the presence of the peptides and occurred in a dose-dependent manner.
Conclusions: The approach described here provides a direction for precise, customised approaches to treat RA and can likely be applied to other systemic autoimmune diseases.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
