![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
Preview |
PDF (Supplementary Materials)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
| Item Type: | Article |
|---|---|
| Title: | Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion |
| Creators: |
Rejeski, K.  ORCID: https://orcid.org/0000-0003-3905-0251, Perez, A., Iacoboni, G. ORCID: https://orcid.org/0000-0003-0805-9288, Blumenberg, V. ORCID: https://orcid.org/0000-0003-1379-0876, Bücklein, V.L. ORCID: https://orcid.org/0000-0001-7391-7280, Völkl, S. ORCID: https://orcid.org/0000-0003-2193-3048, Penack, O., Albanyan, O. ORCID: https://orcid.org/0000-0003-4802-5445, Stock, S. ORCID: https://orcid.org/0000-0002-5072-5013, Müller, F. ORCID: https://orcid.org/0000-0001-5487-5839, Karschnia, P. ORCID: https://orcid.org/0000-0002-1254-5310, Petrera, A., Reid, K. ORCID: https://orcid.org/0000-0002-6585-0781, Faramand, R. ORCID: https://orcid.org/0000-0001-7750-781X, Davila, M.L. ORCID: https://orcid.org/0000-0002-6270-3065, Modi, K. ORCID: https://orcid.org/0000-0003-3351-8829, Dean, E.A. ORCID: https://orcid.org/0000-0003-3153-223X, Bachmeier, C. ORCID: https://orcid.org/0000-0002-9832-3670, von Bergwelt-Baildon, M., Locke, F.L., Bethge, W. ORCID: https://orcid.org/0000-0001-6052-2618, Bullinger, L. ORCID: https://orcid.org/0000-0002-5890-5510, Mackensen, A. ORCID: https://orcid.org/0000-0002-0685-4483, Barba, P. ORCID: https://orcid.org/0000-0003-1038-5197, Jain, M.D. ORCID: https://orcid.org/0000-0002-7789-1257 and Subklewe, M. ORCID: https://orcid.org/0000-0001-9154-9469
|
| Abstract: | Prolonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with "intermittent" neutrophil recovery (e.g., recurrent neutrophil dips) compared to either "quick" or "aplastic" recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion. |
| Keywords: | Signal Transducing Adaptor Proteins, CD19 Antigen, Cell Cycle, Adoptive Immunotherapy, Chimeric Antigen Receptors |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 9 |
| Number: | 38 |
| Page Range: | eadg3919 |
| Date: | 22 September 2023 |
| Official Publication: | https://doi.org/10.1126/sciadv.adg3919 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
