Cargando…

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy

Chimeric antigen receptor (CAR) T cells targeting CD19(+) B cells have demonstrated efficacy in refractory systemic lupus erythematosus (SLE). Although initial clinical data suggest that anti-CD19 CAR T cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T cell t...

Descripción completa

Detalles Bibliográficos
Autores principales: Nunez, Daniel, Patel, Darshil, Volkov, Jenell, Wong, Steven, Vorndran, Zachary, Müller, Fabian, Aigner, Michael, Völkl, Simon, Mackensen, Andreas, Schett, Georg, Basu, Samik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514439/
https://www.ncbi.nlm.nih.gov/pubmed/37744005
http://dx.doi.org/10.1016/j.omtm.2023.08.023
_version_ 1785108728354177024
author Nunez, Daniel
Patel, Darshil
Volkov, Jenell
Wong, Steven
Vorndran, Zachary
Müller, Fabian
Aigner, Michael
Völkl, Simon
Mackensen, Andreas
Schett, Georg
Basu, Samik
author_facet Nunez, Daniel
Patel, Darshil
Volkov, Jenell
Wong, Steven
Vorndran, Zachary
Müller, Fabian
Aigner, Michael
Völkl, Simon
Mackensen, Andreas
Schett, Georg
Basu, Samik
author_sort Nunez, Daniel
collection PubMed
description Chimeric antigen receptor (CAR) T cells targeting CD19(+) B cells have demonstrated efficacy in refractory systemic lupus erythematosus (SLE). Although initial clinical data suggest that anti-CD19 CAR T cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T cell therapy in SLE patients remain unclear. We profiled serum in six refractory SLE patients prior to and 3 months following CAR T cell infusion. Three months post T cell infusion, the inflammatory cytokines IL-6 and TNFα decreased in patient sera. This was accompanied by elevations in serum IL-7 and BAFF. Furthermore, SLE-associated antibodies dropped profoundly in five of six patients. Last, consistent with other reports of CD19 CAR T therapy in B cell malignancies, we were able to show marginal impact of anti-CD19 CART therapy on pre-existing humoral immune responses in SLE patients. Together, these results provide insights into the mechanisms of efficacy of anti-CD19 CAR T cell therapy in SLE.
format Online
Article
Text
id pubmed-10514439
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Society of Gene & Cell Therapy
record_format MEDLINE/PubMed
spelling pubmed-105144392023-09-23 Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy Nunez, Daniel Patel, Darshil Volkov, Jenell Wong, Steven Vorndran, Zachary Müller, Fabian Aigner, Michael Völkl, Simon Mackensen, Andreas Schett, Georg Basu, Samik Mol Ther Methods Clin Dev Brief Report Chimeric antigen receptor (CAR) T cells targeting CD19(+) B cells have demonstrated efficacy in refractory systemic lupus erythematosus (SLE). Although initial clinical data suggest that anti-CD19 CAR T cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T cell therapy in SLE patients remain unclear. We profiled serum in six refractory SLE patients prior to and 3 months following CAR T cell infusion. Three months post T cell infusion, the inflammatory cytokines IL-6 and TNFα decreased in patient sera. This was accompanied by elevations in serum IL-7 and BAFF. Furthermore, SLE-associated antibodies dropped profoundly in five of six patients. Last, consistent with other reports of CD19 CAR T therapy in B cell malignancies, we were able to show marginal impact of anti-CD19 CART therapy on pre-existing humoral immune responses in SLE patients. Together, these results provide insights into the mechanisms of efficacy of anti-CD19 CAR T cell therapy in SLE. American Society of Gene & Cell Therapy 2023-09-01 /pmc/articles/PMC10514439/ /pubmed/37744005 http://dx.doi.org/10.1016/j.omtm.2023.08.023 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Nunez, Daniel
Patel, Darshil
Volkov, Jenell
Wong, Steven
Vorndran, Zachary
Müller, Fabian
Aigner, Michael
Völkl, Simon
Mackensen, Andreas
Schett, Georg
Basu, Samik
Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy
title Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy
title_full Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy
title_fullStr Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy
title_full_unstemmed Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy
title_short Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy
title_sort cytokine and reactivity profiles in sle patients following anti-cd19 cart therapy
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514439/
https://www.ncbi.nlm.nih.gov/pubmed/37744005
http://dx.doi.org/10.1016/j.omtm.2023.08.023
work_keys_str_mv AT nunezdaniel cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT pateldarshil cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT volkovjenell cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT wongsteven cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT vorndranzachary cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT mullerfabian cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT aignermichael cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT volklsimon cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT mackensenandreas cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT schettgeorg cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy
AT basusamik cytokineandreactivityprofilesinslepatientsfollowinganticd19carttherapy