Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time
Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19+ B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1298598/full |
| _version_ | 1797349430376005632 |
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| author | Ivan Odak Lâle M. Bayir Lâle M. Bayir Lennart Riemann Lennart Riemann Ruth Sikora Ruth Sikora Jessica Schneider Jessica Schneider Yankai Xiao Nora Möhn Thomas Skripuletz Gernot Beutel Matthias Eder Arnold Ganser Reinhold Förster Christian R. Schultze-Florey Christian R. Schultze-Florey Christian Koenecke Christian Koenecke |
| author_facet | Ivan Odak Lâle M. Bayir Lâle M. Bayir Lennart Riemann Lennart Riemann Ruth Sikora Ruth Sikora Jessica Schneider Jessica Schneider Yankai Xiao Nora Möhn Thomas Skripuletz Gernot Beutel Matthias Eder Arnold Ganser Reinhold Förster Christian R. Schultze-Florey Christian R. Schultze-Florey Christian Koenecke Christian Koenecke |
| author_sort | Ivan Odak |
| collection | DOAJ |
| description | Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19+ B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity. Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy. |
| first_indexed | 2024-03-08T12:30:08Z |
| format | Article |
| id | doaj.art-5786ca34b273415fb85d64d76fb3aa83 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T12:30:08Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5786ca34b273415fb85d64d76fb3aa832024-01-22T04:41:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.12985981298598Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over timeIvan Odak0Lâle M. Bayir1Lâle M. Bayir2Lennart Riemann3Lennart Riemann4Ruth Sikora5Ruth Sikora6Jessica Schneider7Jessica Schneider8Yankai Xiao9Nora Möhn10Thomas Skripuletz11Gernot Beutel12Matthias Eder13Arnold Ganser14Reinhold Förster15Christian R. Schultze-Florey16Christian R. Schultze-Florey17Christian Koenecke18Christian Koenecke19Institute of Immunology, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyVariability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19+ B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity. Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1298598/fullCAR T-cellDLBCL diffuse large B-cell lymphomaALL acute lymphoblastic leukemiatisagenlecleucel tisa-celspectral flow cytometryimmunophenotyping |
| spellingShingle | Ivan Odak Lâle M. Bayir Lâle M. Bayir Lennart Riemann Lennart Riemann Ruth Sikora Ruth Sikora Jessica Schneider Jessica Schneider Yankai Xiao Nora Möhn Thomas Skripuletz Gernot Beutel Matthias Eder Arnold Ganser Reinhold Förster Christian R. Schultze-Florey Christian R. Schultze-Florey Christian Koenecke Christian Koenecke Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time Frontiers in Immunology CAR T-cell DLBCL diffuse large B-cell lymphoma ALL acute lymphoblastic leukemia tisagenlecleucel tisa-cel spectral flow cytometry immunophenotyping |
| title | Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time |
| title_full | Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time |
| title_fullStr | Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time |
| title_full_unstemmed | Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time |
| title_short | Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time |
| title_sort | brief research report in depth immunophenotyping reveals stability of cd19 car t cells over time |
| topic | CAR T-cell DLBCL diffuse large B-cell lymphoma ALL acute lymphoblastic leukemia tisagenlecleucel tisa-cel spectral flow cytometry immunophenotyping |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1298598/full |
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