Tripterygium glycosides as a potential treatment for CAR-T induced cytokine release syndrome: implication of monocyte depletion
Posted 27 Nov 2020
medRxiv DOI: 10.1101/2020.11.22.20232801
Posted 27 Nov 2020
Background Cytokine release syndrome (CRS) is a potentially life-threatening complication of chimeric antigen receptor T (CAR-T) cell therapy. Recent studies indicated critical roles of macrophages and monocytes in CAR-T induced CRS. Here, we report rapid dissipation of CAR-T induced CRS in two patients after receiving Tripterygium glycosides (TG). Effects of triptolide, the major active component of TG, on macrophages and monocytes were examined in animal models. Methods Two patients with CRS after CAR-T cell therapy (for hematological malignancy) received TG (50 mg, p.o.). Flow cytometry analysis and single cell RNA sequencing (scRNAseq) were conducted to examine the effects of TG on immune cells. Potential effects of triptolide were also examined ex vivo using patient-derived monocytes, as well as in mice. Findings Rapid alleviation of fever and cytokine storm was observed within 72 hours after TG treatment. Blood concentration of triptolide ranged from 21 to 154 ng/mL during treatment. Flow cytometry and scRNAseq showed selective depletion of monocytes with minimal impact on CAR-T cells in both patients. In ex vivo experiments with patient-derived monocytes, triptolide dramatically inhibited the synthesis of pro-inflammatory cytokines (e.g., IL-6, IL-10, and IP-10). Triptolide also rapidly and selectively depleted peritoneal concanavalin A activated macrophages and monocytes in mice. Interpretation TG could be a promising treatment for CAR-T induced CRS, as well as other diseases with similar mechanisms, e.g., hemophagocytic lymphohistiocytosis and COVID-19. Our preliminary findings require further verification with properly designed clinical trials.
- Downloaded 210 times
- Download rankings, all-time:
- Site-wide: 104,397
- In hematology: 73
- Year to date:
- Site-wide: 17,389
- Since beginning of last month:
- Site-wide: 17,397
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!