GPIbα CAAR-T cells function like a Trojan horse to eliminate autoreactive B cells to treat immune thrombocytopenia
Breakthrough treatment for refractory and relapsed immune thrombocytopenia (ITP) patients is urgently needed. Autoantibody-mediated platelet clearance and megakaryocyte dysfunction are important pathogenic mediators of ITP. Glycoprotein (GP) Ibα is a significant autoantigen found in ITP patients and is associated with poor response to standard immunosuppressive treatments. Here, we engineered human T cells to express a chimeric autoantibody receptor (CAAR) with GPIbα constructed into the ligand-binding domain fused to the CD8 transmembrane domain and CD3ζ-4-1BB signaling domains. We performed cytotoxicity assays to assess GPIbα CAAR-T-cell selective cytolysis of cells expressing anti-GPIbα B-cell receptors (BCRs) in vitro. Furthermore, we demonstrated the potential of GPIbα CAAR-T cells to persist and precisely eliminate GPIbα-specific B cells in vivo. In summary, we present a proof of concept for CAAR-T-cell therapy to eradicate autoimmune B cells while sparing healthy B cells with GPIbα CAAR-T cells that function like a Trojan horse. GPIbα CAAR-Tcell therapy is a promising treatment for refractory and relapsed ITP patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Haematologica - (2024) vom: 01. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Jie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 01.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.3324/haematol.2023.283874 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367889137 |
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| 520 | |a Breakthrough treatment for refractory and relapsed immune thrombocytopenia (ITP) patients is urgently needed. Autoantibody-mediated platelet clearance and megakaryocyte dysfunction are important pathogenic mediators of ITP. Glycoprotein (GP) Ibα is a significant autoantigen found in ITP patients and is associated with poor response to standard immunosuppressive treatments. Here, we engineered human T cells to express a chimeric autoantibody receptor (CAAR) with GPIbα constructed into the ligand-binding domain fused to the CD8 transmembrane domain and CD3ζ-4-1BB signaling domains. We performed cytotoxicity assays to assess GPIbα CAAR-T-cell selective cytolysis of cells expressing anti-GPIbα B-cell receptors (BCRs) in vitro. Furthermore, we demonstrated the potential of GPIbα CAAR-T cells to persist and precisely eliminate GPIbα-specific B cells in vivo. In summary, we present a proof of concept for CAAR-T-cell therapy to eradicate autoimmune B cells while sparing healthy B cells with GPIbα CAAR-T cells that function like a Trojan horse. GPIbα CAAR-Tcell therapy is a promising treatment for refractory and relapsed ITP patients | ||
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| 700 | 1 | |a Huang, Linlin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Junling |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Mei, Heng |e verfasserin |4 aut | |
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