| |  Online-Ressource |
|---|
| Verfasst von: | Yang, Mingya [VerfasserIn]  |
|---|
| | Wang, Lei [VerfasserIn] |
|---|
| | Neuber, Brigitte [VerfasserIn] |
|---|
| | Wang, Sanmei [VerfasserIn] |
|---|
| | Sauer, Tim [VerfasserIn] |
|---|
| | Sellner, Leopold [VerfasserIn] |
|---|
| | Schubert, Maria-Luisa [VerfasserIn] |
|---|
| | Hückelhoven-Krauss, Angela [VerfasserIn] |
|---|
| | Kleist, Christian [VerfasserIn] |
|---|
| | Eckstein, Volker [VerfasserIn] |
|---|
| | Müller-Tidow, Carsten [VerfasserIn] |
|---|
| | Dreger, Peter [VerfasserIn] |
|---|
| | Schmitt, Michael [VerfasserIn] |
|---|
| | Schmitt, Anita [VerfasserIn] |
|---|
| Titel: | Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells |
|---|
| Verf.angabe: | Mingya Yang, Lei Wang, Ming Ni, Brigitte Neuber, Sanmei Wang, Wenjie Gong, Tim Sauer, Leopold Sellner, Maria-Luisa Schubert, Angela Hückelhoven-Krauss, Jian Hong, Lixin Zhu, Christian Kleist, Volker Eckstein, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt and Anita Schmitt |
|---|
| E-Jahr: | 2020 |
|---|
| Jahr: | 09 December 2020 |
|---|
| Umfang: | 14 S. |
|---|
| Fussnoten: | Gesehen am 17.12.2020 |
|---|
| Titel Quelle: | Enthalten in: Frontiers in immunology |
|---|
| Ort Quelle: | Lausanne : Frontiers Media, 2010 |
|---|
| Jahr Quelle: | 2020 |
|---|
| Band/Heft Quelle: | 11(2020), Artikel-ID 608167, Seite 1-14 |
|---|
| ISSN Quelle: | 1664-3224 |
|---|
| Abstract: | Chimeric antigen receptor (CAR) T cell therapy has shown promising responses in patients with refractory or relapsed aggressive B-cell malignancies that are resistant to conventional chemotherapy or stem cell transplantation. A potentially combinatorial therapeutic strategy may be the inhibition of anti-apoptotic Bcl-2 family proteins, overexpressed in most cancer cells. In this study we investigated the combination of 3rd generation CD19.CAR-T cells and the BH3 mimetics venetoclax, a Bcl-2 inhibitor, and S63845, a Mcl-1 inhibitor, under three different treatment conditions: pre-sensitization of cancer cells with BH3 mimetics followed by CAR-T cell treatment, simultaneous combination therapy, and the administration of BH3 mimetics after CAR-T cell treatment. Our results showed that administration of CAR-T cells and BH3 mimetics had a significant effect on the quantity and quality of CD19.CAR-T cells. The administration of BH3 mimetics prior to CAR-T cell therapy exerted an enhanced cytotoxic efficacy by upregulating the CD19 expression and pro-apoptotic proteins in highly sensitive tumor cells, and thereby improving both CD19.CAR-T cell cytotoxicity and persistence. In simultaneous and post-treatment approaches, however, the quantity of CAR-T cells was adversely affected. Our findings indicate pre-sensitization of highly sensitive tumor cells with BH3 mimetics could enhance the cytotoxic efficacy of CAR-T cell treatment. |
|---|
| DOI: | doi:10.3389/fimmu.2020.608167 |
|---|
| URL: | kostenfrei: Volltext: https://doi.org/10.3389/fimmu.2020.608167 |
|---|
| | kostenfrei: Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2020.608167/full |
|---|
| | DOI: https://doi.org/10.3389/fimmu.2020.608167 |
|---|
| Datenträger: | Online-Ressource |
|---|
| Sprache: | eng |
|---|
| K10plus-PPN: | 174312144X |
|---|
| Verknüpfungen: | → Zeitschrift |
|---|
| |
|
|---|
| | |
|---|
| Lokale URL UB: |  Zum Volltext |
|---|
Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells / Yang, Mingya [VerfasserIn]; 09 December 2020 (Online-Ressource)
