Article ; Online: Early induction of cytokine release syndrome by rapidly generated CAR T cells in preclinical models.
2024 Volume 16, Issue 4, Page(s) 784–804
Abstract: Cytokine release syndrome (CRS) is a significant side-effect of conventional chimeric antigen receptor (CAR) T-cell therapy. To facilitate patient accessibility, short-term (st) CAR T cells, which are administered to patients only 24 h after vector ... ...
| Abstract | Cytokine release syndrome (CRS) is a significant side-effect of conventional chimeric antigen receptor (CAR) T-cell therapy. To facilitate patient accessibility, short-term (st) CAR T cells, which are administered to patients only 24 h after vector exposure, are in focus of current investigations. Their impact on the incidence and severity of CRS has been poorly explored. Here, we evaluated CD19-specific stCAR T cells in preclinical models. In co-culture with tumor cells and monocytes, stCAR T cells exhibited anti-tumoral activity and potent release of CRS-related cytokines (IL-6, IFN-γ, TNF-α, GM-CSF, IL-2, IL-10). When administered to NSG-SGM3 mice, stCAR T cells, but not conventional CAR T cells, induced severe acute adverse events within 24 h, including hypothermia and weight loss, as well as high body scores, independent of the presence of tumor target cells. Human (IFN-γ, TNF-α, IL-2, IL-10) and murine (MCP-1, IL-6, G-CSF) cytokines, typical for severe CRS, were systemically elevated. Our data highlight potential safety risks of rapidly manufactured CAR T cells and suggest NSG-SGM3 mice as sensitive model for their preclinical safety evaluation. |
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| MeSH term(s) | Humans ; Animals ; Mice ; Cytokine Release Syndrome ; Interleukin-10 ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Interleukin-2 ; Cytokines ; Immunotherapy, Adoptive ; T-Lymphocytes ; Neoplasms |
| Chemical Substances | Interleukin-10 (130068-27-8) ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Interleukin-2 ; Cytokines |
| Language | English |
| Publishing date | 2024-03-21 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2467145-9 |
| ISSN | 1757-4684 ; 1757-4676 |
| ISSN (online) | 1757-4684 |
| ISSN | 1757-4676 |
| DOI | 10.1038/s44321-024-00055-9 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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