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000286660 1001_ $$aSoto, Karla E G$$b0
000286660 245__ $$aTargeting colorectal cancer cells using AND-gated adaptor RevCAR T-cells.
000286660 260__ $$aLausanne$$bFrontiers Media$$c2023
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000286660 520__ $$aDespite the success of chimeric antigen receptor (CAR) T-cells especially for treating hematological malignancies, critical drawbacks, such as 'on-target, off-tumor' toxicities, need to be addressed to improve safety in translating to clinical application. This is especially true, when targeting tumor-associated antigens (TAAs) that are not exclusively expressed by solid tumors but also on hea9lthy tissues. To improve the safety profile, we developed switchable adaptor CAR systems including the RevCAR system. RevCAR T-cells are activated by cross-linking of bifunctional adaptor molecules termed target modules (RevTM). In a further development, we established a Dual-RevCAR system for an AND-gated combinatorial targeting by splitting the stimulatory and co-stimulatory signals of the RevCAR T-cells on two individual CARs. Examples of common markers for colorectal cancer (CRC) are the carcinoembryonic antigen (CEA) and the epithelial cell adhesion molecule (EpCAM), while these antigens are also expressed by healthy cells. Here we describe four novel structurally different RevTMs for targeting of CEA and EpCAM. All anti-CEA and anti-EpCAM RevTMs were validated and the simultaneous targeting of CEA+ and EpCAM+ cancer cells redirected specific in vitro and in vivo killing by Dual-RevCAR T-cells. In summary, we describe the development of CEA and EpCAM specific adaptor RevTMs for monospecific and AND-gated targeting of CRC cells via the RevCAR platform as an improved approach to increase tumor specificity and safety of CAR T-cell therapies.
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000286660 650_7 $$2Other$$aAND-gate targeting
000286660 650_7 $$2Other$$aCAR T-cells
000286660 650_7 $$2Other$$aCEA
000286660 650_7 $$2Other$$aEpCAM
000286660 650_7 $$2Other$$acolorectal cancer
000286660 7001_ $$aLoureiro, Liliana R$$b1
000286660 7001_ $$aBartsch, Tabea$$b2
000286660 7001_ $$aArndt, Claudia$$b3
000286660 7001_ $$aKegler, Alexandra$$b4
000286660 7001_ $$aMitwasi, Nicola$$b5
000286660 7001_ $$aDrewitz, Laura$$b6
000286660 7001_ $$aHoffmann, Lydia$$b7
000286660 7001_ $$aSaleh, Haidy A$$b8
000286660 7001_ $$aCrespo, Eugenia$$b9
000286660 7001_ $$aMehnert, Maria$$b10
000286660 7001_ $$aDaglar, Cansu$$b11
000286660 7001_ $$aAbken, Hinrich$$b12
000286660 7001_ $$0P:(DE-He78)b2290261145f21c46f2d42783c69d104$$aMomburg, Frank$$b13$$udkfz
000286660 7001_ $$0P:(DE-HGF)0$$aBachmann, Michael$$b14
000286660 7001_ $$0P:(DE-HGF)0$$aFeldmann, Anja$$b15
000286660 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2023.1302354$$gVol. 14, p. 1302354$$p1302354$$tFrontiers in immunology$$v14$$x1664-3224$$y2023
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