Fully human anti-CD19 CAR T cells derived from systemic lupus erythematosus patients exhibit cytotoxicity with reduced inflammatory cytokine production.
Chimeric antigen receptor
Cytokines
Systemic Lupus Erythematosus
Journal
Transplantation and cellular therapy
ISSN: 2666-6367
Titre abrégé: Transplant Cell Ther
Pays: United States
ID NLM: 101774629
Informations de publication
Date de publication:
26 Mar 2024
26 Mar 2024
Historique:
received:
13
11
2023
revised:
14
03
2024
accepted:
22
03
2024
medline:
29
3
2024
pubmed:
29
3
2024
entrez:
28
3
2024
Statut:
aheadofprint
Résumé
KYV-101 is an autologous anti-CD19 chimeric antigen receptor (CAR)-T cell therapy under investigation for patients with B-cell driven autoimmune diseases. Hu19-CD828Z is a fully human anti-CD19 CAR designed and demonstrated to have a favorable clinical safety profile. Since anti-CD19 CAR T cells target and kill B cells in both circulation and tissues, the treatment with Hu19-CD828Z CAR T cells offers great potential in depleting autoreactive B cells. Demonstrate that Hu19-CD828Z CAR T cells manufactured from cryopreserved leukaphereses from patients with systemic lupus erythematosus (SLE) exhibit CAR-mediated and CD19-dependent cytokine release, proliferation and cytotoxicity when co-cultured with autologous primary B cells. T cells were enriched from cryopreserved leukaphereses from SLE patients or healthy donors (HD). CAR T cells were generated by transducing these cells with a lentiviral vector encoding Hu19-CD828Z. CAR-mediated and CD19-dependent activity was monitored in vitro in a set of cytotoxicity, cytokine release and proliferation studies, in response to autologous primary CD19 Hu19-CD828Z CAR T cells produced from SLE patients or HD induced greater proliferation and dose-dependent cytotoxicity against both autologous primary B cells and the CD19 Hu19-CD828Z CAR T cells generated from SLE patient lymphocytes demonstrate CAR-mediated and CD19-dependent activity against autologous primary B cells with reduced inflammatory cytokine production supporting KYV-101 as a novel potential therapy for the depletion of pathogenic B cells in SLE patients.
Sections du résumé
BACKGROUND
BACKGROUND
KYV-101 is an autologous anti-CD19 chimeric antigen receptor (CAR)-T cell therapy under investigation for patients with B-cell driven autoimmune diseases. Hu19-CD828Z is a fully human anti-CD19 CAR designed and demonstrated to have a favorable clinical safety profile. Since anti-CD19 CAR T cells target and kill B cells in both circulation and tissues, the treatment with Hu19-CD828Z CAR T cells offers great potential in depleting autoreactive B cells.
OBJECTIVE
OBJECTIVE
Demonstrate that Hu19-CD828Z CAR T cells manufactured from cryopreserved leukaphereses from patients with systemic lupus erythematosus (SLE) exhibit CAR-mediated and CD19-dependent cytokine release, proliferation and cytotoxicity when co-cultured with autologous primary B cells.
STUDY DESIGN
METHODS
T cells were enriched from cryopreserved leukaphereses from SLE patients or healthy donors (HD). CAR T cells were generated by transducing these cells with a lentiviral vector encoding Hu19-CD828Z. CAR-mediated and CD19-dependent activity was monitored in vitro in a set of cytotoxicity, cytokine release and proliferation studies, in response to autologous primary CD19
RESULTS
RESULTS
Hu19-CD828Z CAR T cells produced from SLE patients or HD induced greater proliferation and dose-dependent cytotoxicity against both autologous primary B cells and the CD19
CONCLUSION
CONCLUSIONS
Hu19-CD828Z CAR T cells generated from SLE patient lymphocytes demonstrate CAR-mediated and CD19-dependent activity against autologous primary B cells with reduced inflammatory cytokine production supporting KYV-101 as a novel potential therapy for the depletion of pathogenic B cells in SLE patients.
Identifiants
pubmed: 38548226
pii: S2666-6367(24)00297-5
doi: 10.1016/j.jtct.2024.03.023
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest S.P., C.D.K., J.K.C., T.V.B. are or were employees of Kyverna Therapeutics when this study was conducted. J.D., J.T., I.M., M.A., G.S., A.M., and G.L.-G. report no conflicts of interest.