Digital-droplet PCR for quantification of CD19-directed CAR T-cells
- CD19-directed CAR-T-cells (CD19-CAR) have demonstrated remarkable clinical results in patients suffering from refractory or relapsed lymphoma and acute lymphoblastic leukemia. In order to further optimize follow-up, to explain treatment failure, and to control adverse events biomarkers for monitoring of response are urgently needed. Peak expansion and persistence are correlated with response rates and severity of side effects. However, no standardized method or commercially assay for CD19-CAR measurement is established yet. In this study, two primer-probe assays for digital-droplet PCR (ddPCR) were designed and subsequently explored on 54 samples collected from seven patients after CD19-CAR treatment with axi-cel over time. Detection and quantification of CAR-T-cells were feasible and reliable for all patients included. Peak expansion measured with our assay significantly correlated with the grade of neurologic adverse events but not with cytokine release syndrome. All patients with loss of CAR-signal eventually had disease progression. In summary, our novel assay allows monitoring of CAR-T-cells \(\textit {in vivo}\) and may add to safety and efficacy of CAR-T treatment.
Author: | Thomas MikaORCiDGND, Abdelouahid MaghnoujGND, Susanne Klein-ScoryORCiDGND, Swetlana Ladigan-BaduraORCiDGND, Alexander BaraniskinGND, Julia ThomsonGND, Justin HasenkampGND, Stephan HahnORCiDGND, Gerald WulfGND, Roland SchroersORCiDGND |
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URN: | urn:nbn:de:hbz:294-73962 |
DOI: | https://doi.org/10.3389/fmolb.2020.00084 |
Parent Title (English): | Frontiers in molecular biosciences |
Publisher: | Frontiers |
Place of publication: | Lausanne |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2020/08/07 |
Date of first Publication: | 2020/05/15 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds CD19-directed chimeric antigen receptor (CAR) T-cells; aggressive lymphoma; axicabtagene ciloleucel; digital-droplet PCR (ddPCR); flow cytometry (FCM); immunotherapy |
Volume: | 7 |
Issue: | Article 84 |
First Page: | 84-1 |
Last Page: | 84-9 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Knappschaftskrankenhaus Bochum, Medizinische Klinik |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |