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Status: Bibliographieeintrag

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Verfasst von:Soto, Karla E. G. [VerfasserIn]   i
 Loureiro, Liliana R. [VerfasserIn]   i
 Bartsch, Tabea [VerfasserIn]   i
 Arndt, Claudia [VerfasserIn]   i
 Mitwasi, Nicola [VerfasserIn]   i
 Drewitz, Laura [VerfasserIn]   i
 Saleh, Haidy A. [VerfasserIn]   i
 Mehnert, Maria [VerfasserIn]   i
 Abken, Hinrich [VerfasserIn]   i
 Momburg, Frank [VerfasserIn]   i
 Bachmann, Michael [VerfasserIn]   i
 Feldmann, Anja [VerfasserIn]   i
Titel:Targeting colorectal cancer cells using AND-gated adaptor RevCAR T-cells
Verf.angabe:Karla E.G. Soto, Liliana R. Loureiro, Tabea Bartsch, Claudia Arndt, Nicola Mitwasi, Laura Drewitz, Haidy A. Saleh, Maria Mehnert, Hinrich Abken, Frank Momburg, Michael Bachmann and Anja Feldmann
E-Jahr:2023
Jahr:15 December 2023
Umfang:16 S.
Fussnoten:Gesehen am 15.03.2024
Titel Quelle:Enthalten in: Frontiers in immunology
Ort Quelle:Lausanne : Frontiers Media, 2010
Jahr Quelle:2023
Band/Heft Quelle:14(2023) vom: Dez., Artikel-ID 1302354, Seite 1-16
ISSN Quelle:1664-3224
Abstract:Despite the success of chimeric antigen receptor (CAR) T-cells especially for treating hematological malignancies, critical drawbacks, such as “on-target, off-tumor” toxicities, need to be addressed to improve safety in translating to clinical application. This is especially true, when targeting tumor-associated antigens (TAAs) that are not exclusively expressed by solid tumors but also on hea9lthy tissues. To improve the safety profile, we developed switchable adaptor CAR systems including the RevCAR system. RevCAR T-cells are activated by cross-linking of bifunctional adaptor molecules termed target modules (RevTM). In a further development, we established a Dual-RevCAR system for an AND-gated combinatorial targeting by splitting the stimulatory and co-stimulatory signals of the RevCAR T-cells on two individual CARs. Examples of common markers for colorectal cancer (CRC) are the carcinoembryonic antigen (CEA) and the epithelial cell adhesion molecule (EpCAM), while these antigens are also expressed by healthy cells. Here we describe four novel structurally different RevTMs for targeting of CEA and EpCAM. All anti-CEA and anti-EpCAM RevTMs were validated and the simultaneous targeting of CEA+ and EpCAM+ cancer cells redirected specific in vitro and in vivo killing by Dual-RevCAR T-cells. In summary, we describe the development of CEA and EpCAM specific adaptor RevTMs for monospecific and AND-gated targeting of CRC cells via the RevCAR platform as an improved approach to increase tumor specificity and safety of CAR T-cell therapies.
DOI:doi:10.3389/fimmu.2023.1302354
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.3389/fimmu.2023.1302354
 Volltext: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1302354/full
 DOI: https://doi.org/10.3389/fimmu.2023.1302354
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:AND-gate targeting
 CAR T-cells
 CEA
 colorectal cancer
 EpCAM
K10plus-PPN:1883479274
Verknüpfungen:→ Zeitschrift

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