Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model
The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
21 Jul 2017
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| In: |
OncoImmunology
Year: 2017, Jahrgang: 6, Heft: 10 |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2017.1342909 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1080/2162402X.2017.1342909
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| Verfasserangaben: | Elham Pishali Bejestani, Marc Cartellieri, Ralf Bergmann, Armin Ehninger, Simon Loff, Michael Kramer, Johannes Spehr, Antje Dietrich, Anja Feldmann, Susann Albert, Martin Wermke, Michael Baumann, Mechthild Krause, Martin Bornhäuser, Gerhard Ehninger, Michael Bachmann & Malte von Bonin |
MARC
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| 245 | 1 | 0 | |a Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model |c Elham Pishali Bejestani, Marc Cartellieri, Ralf Bergmann, Armin Ehninger, Simon Loff, Michael Kramer, Johannes Spehr, Antje Dietrich, Anja Feldmann, Susann Albert, Martin Wermke, Michael Baumann, Mechthild Krause, Martin Bornhäuser, Gerhard Ehninger, Michael Bachmann & Malte von Bonin |
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| 520 | |a The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model. In addition, we analyzed phenotypic and functional changes of cancer cells and UniCAR-T cells in association with the administration of the targeting module to reveal potential immunoevasive mechanisms. Most notably, UniCAR-T cell activation induced upregulation of immune-inhibitory molecules such as programmed death ligands. In conclusion, this work illustrates that the UniCAR platform mediates potent anti-tumor activity in a relevant in vitro and in vivo solid tumor model. | ||
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