Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
09 December 2020
|
| In: |
Frontiers in immunology
Year: 2020, Volume: 11, Pages: 1-14 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.608167 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2020.608167 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2020.608167/full 
|
| Author Notes: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 174312144X | ||
| 003 | DE-627 | ||
| 005 | 20240807124053.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201217s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2020.608167 |2 doi | |
| 035 | |a (DE-627)174312144X | ||
| 035 | |a (DE-599)KXP174312144X | ||
| 035 | |a (OCoLC)1264393464 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Yang, Mingya |d 1989- |e VerfasserIn |0 (DE-588)117476788X |0 (DE-627)1045595365 |0 (DE-576)51592282X |4 aut | |
| 245 | 1 | 0 | |a Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells |c 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 |
| 246 | 3 | 3 | |a Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19. CAR-T Cells |
| 264 | 1 | |c 09 December 2020 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 17.12.2020 | ||
| 520 | |a 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. | ||
| 700 | 1 | |a Wang, Lei |d 1985- |e VerfasserIn |0 (DE-588)1076031994 |0 (DE-627)834093308 |0 (DE-576)444802398 |4 aut | |
| 700 | 1 | |a Neuber, Brigitte |d 1974- |e VerfasserIn |0 (DE-588)1052913563 |0 (DE-627)789293188 |0 (DE-576)408653884 |4 aut | |
| 700 | 1 | |a Wang, Sanmei |d 1990- |e VerfasserIn |0 (DE-588)1191709442 |0 (DE-627)1670170527 |4 aut | |
| 700 | 1 | |a Sauer, Tim |d 1981- |e VerfasserIn |0 (DE-588)138282013 |0 (DE-627)601099516 |0 (DE-576)307058166 |4 aut | |
| 700 | 1 | |a Sellner, Leopold |d 1984- |e VerfasserIn |0 (DE-588)143493825 |0 (DE-627)646576704 |0 (DE-576)337362963 |4 aut | |
| 700 | 1 | |a Schubert, Maria-Luisa |d 1982- |e VerfasserIn |0 (DE-588)1147867631 |0 (DE-627)1007273801 |0 (DE-576)49608089X |4 aut | |
| 700 | 1 | |a Hückelhoven-Krauss, Angela |d 1983- |e VerfasserIn |0 (DE-588)1034095889 |0 (DE-627)744057280 |0 (DE-576)381742822 |4 aut | |
| 700 | 1 | |a Kleist, Christian |e VerfasserIn |0 (DE-588)138977410 |0 (DE-627)703170287 |0 (DE-576)309272971 |4 aut | |
| 700 | 1 | |a Eckstein, Volker |d 1957- |e VerfasserIn |0 (DE-588)172851408 |0 (DE-627)697780732 |0 (DE-576)133707059 |4 aut | |
| 700 | 1 | |a Müller-Tidow, Carsten |d 1968- |e VerfasserIn |0 (DE-588)1015101798 |0 (DE-627)705330230 |0 (DE-576)351197893 |4 aut | |
| 700 | 1 | |a Dreger, Peter |e VerfasserIn |0 (DE-588)1028891881 |0 (DE-627)732699894 |0 (DE-576)376320966 |4 aut | |
| 700 | 1 | |a Schmitt, Michael |d 1966- |e VerfasserIn |0 (DE-588)133177173 |0 (DE-627)538000600 |0 (DE-576)299672921 |4 aut | |
| 700 | 1 | |a Schmitt, Anita |d 1969- |e VerfasserIn |0 (DE-588)141722495 |0 (DE-627)630587752 |0 (DE-576)325593892 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d Lausanne : Frontiers Media, 2010 |g 11(2020), Artikel-ID 608167, Seite 1-14 |h Online-Ressource |w (DE-627)657998354 |w (DE-600)2606827-8 |w (DE-576)343624834 |x 1664-3224 |7 nnas |a Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells |
| 773 | 1 | 8 | |g volume:11 |g year:2020 |g elocationid:608167 |g pages:1-14 |g extent:14 |a Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells |
| 856 | 4 | 0 | |u https://doi.org/10.3389/fimmu.2020.608167 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fimmu.2020.608167/full |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20201217 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 141722495 |a Schmitt, Anita |m 141722495:Schmitt, Anita |d 910000 |d 910100 |e 910000PS141722495 |e 910100PS141722495 |k 0/910000/ |k 1/910000/910100/ |p 18 |y j | ||
| 998 | |g 133177173 |a Schmitt, Michael |m 133177173:Schmitt, Michael |d 910000 |d 910100 |e 910000PS133177173 |e 910100PS133177173 |k 0/910000/ |k 1/910000/910100/ |p 17 | ||
| 998 | |g 1028891881 |a Dreger, Peter |m 1028891881:Dreger, Peter |d 910000 |d 910100 |e 910000PD1028891881 |e 910100PD1028891881 |k 0/910000/ |k 1/910000/910100/ |p 16 | ||
| 998 | |g 1015101798 |a Müller-Tidow, Carsten |m 1015101798:Müller-Tidow, Carsten |d 910000 |d 910100 |e 910000PM1015101798 |e 910100PM1015101798 |k 0/910000/ |k 1/910000/910100/ |p 15 | ||
| 998 | |g 172851408 |a Eckstein, Volker |m 172851408:Eckstein, Volker |d 910000 |d 910100 |e 910000PE172851408 |e 910100PE172851408 |k 0/910000/ |k 1/910000/910100/ |p 14 | ||
| 998 | |g 138977410 |a Kleist, Christian |m 138977410:Kleist, Christian |d 910000 |d 911400 |e 910000PK138977410 |e 911400PK138977410 |k 0/910000/ |k 1/910000/911400/ |p 13 | ||
| 998 | |g 1034095889 |a Hückelhoven-Krauss, Angela |m 1034095889:Hückelhoven-Krauss, Angela |d 910000 |d 910100 |e 910000PH1034095889 |e 910100PH1034095889 |k 0/910000/ |k 1/910000/910100/ |p 10 | ||
| 998 | |g 1147867631 |a Schubert, Maria-Luisa |m 1147867631:Schubert, Maria-Luisa |d 910000 |d 910100 |e 910000PS1147867631 |e 910100PS1147867631 |k 0/910000/ |k 1/910000/910100/ |p 9 | ||
| 998 | |g 143493825 |a Sellner, Leopold |m 143493825:Sellner, Leopold |d 50000 |e 50000PS143493825 |k 0/50000/ |p 8 | ||
| 998 | |g 138282013 |a Sauer, Tim |m 138282013:Sauer, Tim |d 910000 |d 910100 |e 910000PS138282013 |e 910100PS138282013 |k 0/910000/ |k 1/910000/910100/ |p 7 | ||
| 998 | |g 1191709442 |a Wang, Sanmei |m 1191709442:Wang, Sanmei |d 50000 |e 50000PW1191709442 |k 0/50000/ |p 5 | ||
| 998 | |g 1052913563 |a Neuber, Brigitte |m 1052913563:Neuber, Brigitte |d 910000 |d 910100 |e 910000PN1052913563 |e 910100PN1052913563 |k 0/910000/ |k 1/910000/910100/ |p 4 | ||
| 998 | |g 1076031994 |a Wang, Lei |m 1076031994:Wang, Lei |p 2 | ||
| 998 | |g 117476788X |a Yang, Mingya |m 117476788X:Yang, Mingya |p 1 |x j | ||
| 999 | |a KXP-PPN174312144X |e 3826567897 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"role":"aut","family":"Yang","given":"Mingya","display":"Yang, Mingya"},{"family":"Wang","display":"Wang, Lei","given":"Lei","role":"aut"},{"given":"Brigitte","display":"Neuber, Brigitte","family":"Neuber","role":"aut"},{"display":"Wang, Sanmei","given":"Sanmei","family":"Wang","role":"aut"},{"role":"aut","display":"Sauer, Tim","given":"Tim","family":"Sauer"},{"role":"aut","family":"Sellner","given":"Leopold","display":"Sellner, Leopold"},{"role":"aut","family":"Schubert","display":"Schubert, Maria-Luisa","given":"Maria-Luisa"},{"role":"aut","family":"Hückelhoven-Krauss","given":"Angela","display":"Hückelhoven-Krauss, Angela"},{"role":"aut","family":"Kleist","display":"Kleist, Christian","given":"Christian"},{"role":"aut","given":"Volker","display":"Eckstein, Volker","family":"Eckstein"},{"display":"Müller-Tidow, Carsten","given":"Carsten","family":"Müller-Tidow","role":"aut"},{"family":"Dreger","given":"Peter","display":"Dreger, Peter","role":"aut"},{"family":"Schmitt","display":"Schmitt, Michael","given":"Michael","role":"aut"},{"role":"aut","family":"Schmitt","display":"Schmitt, Anita","given":"Anita"}],"name":{"displayForm":["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"]},"origin":[{"dateIssuedDisp":"09 December 2020","dateIssuedKey":"2020"}],"recId":"174312144X","title":[{"title":"Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells","title_sort":"Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T Cells"}],"language":["eng"],"titleAlt":[{"title":"Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19. CAR-T Cells"}],"physDesc":[{"extent":"14 S."}],"id":{"doi":["10.3389/fimmu.2020.608167"],"eki":["174312144X"]},"type":{"media":"Online-Ressource","bibl":"article-journal"},"note":["Gesehen am 17.12.2020"],"relHost":[{"disp":"Pre-sensitization of Malignant B Cells through Venetoclax significantly improves the cytotoxic efficacy of CD19.CAR-T CellsFrontiers in immunology","recId":"657998354","language":["eng"],"type":{"media":"Online-Ressource","bibl":"periodical"},"pubHistory":["1.2010 -"],"origin":[{"dateIssuedDisp":"2010-","publisher":"Frontiers Media","publisherPlace":"Lausanne","dateIssuedKey":"2010"}],"title":[{"title":"Frontiers in immunology","title_sort":"Frontiers in immunology"}],"physDesc":[{"extent":"Online-Ressource"}],"part":{"text":"11(2020), Artikel-ID 608167, Seite 1-14","volume":"11","year":"2020","extent":"14","pages":"1-14"},"id":{"eki":["657998354"],"zdb":["2606827-8"],"issn":["1664-3224"]},"note":["Gesehen am 07.11.13"]}]} | ||
| SRT | |a YANGMINGYAPRESENSITI0920 | ||