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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2023
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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 |
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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 |
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