> Details

Yang, Mingya [Author]; Wang, Lei [Author]; Neuber, Brigitte [Author]; Wang, Sanmei [Author]; Sauer, Tim [Author]; Sellner, Leopold [Author]; Schubert, Maria-Luisa [Author]; Hückelhoven-Krauss, Angela [Author]; Kleist, Christian [Author]; Eckstein, Volker [Author]; Müller-Tidow, Carsten [Author]; Dreger, Peter [Author]; Schmitt, Michael [Author]; Schmitt, Anita [Author]

Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells
  • Contributor: 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]
  • imprint: 09 December 2020
  • Published in: Frontiers in immunology ; 11(2020) Artikel-Nummer 608167, 11 Seiten
  • Language: English
  • DOI: 10.3389/fimmu.2020.608167
  • ISSN: 1664-3224
  • Identifier:
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access