PMC:7426526 / 68961-70866 JSONTXT

{"project":"TEST0","denotations":[{"id":"32849491-134-141-3396656","span":{"begin":134,"end":137},"obj":"[\"27427982\"]"},{"id":"32849491-222-229-3396657","span":{"begin":222,"end":225},"obj":"[\"29016929\"]"},{"id":"32849491-225-232-3396658","span":{"begin":453,"end":456},"obj":"[\"29016929\"]"},{"id":"32849491-184-190-3396659","span":{"begin":643,"end":645},"obj":"[\"28270302\"]"},{"id":"32849491-188-195-3396660","span":{"begin":647,"end":650},"obj":"[\"30666307\"]"},{"id":"32849491-143-150-3396661","span":{"begin":796,"end":799},"obj":"[\"30666307\", \"30984613\", \"31907405\", \"31091431\", \"29706540\"]"},{"id":"32849491-195-202-3396662","span":{"begin":1001,"end":1004},"obj":"[\"30666307\"]"},{"id":"32849491-200-207-3396663","span":{"begin":1006,"end":1009},"obj":"[\"31091431\"]"},{"id":"32849491-205-212-3396664","span":{"begin":1011,"end":1014},"obj":"[\"29706540\"]"},{"id":"32849491-204-211-3396665","span":{"begin":1221,"end":1224},"obj":"[\"31091431\"]"},{"id":"32849491-209-216-3396666","span":{"begin":1226,"end":1229},"obj":"[\"29706540\"]"},{"id":"32849491-98-105-3396667","span":{"begin":1330,"end":1333},"obj":"[\"27138041\"]"},{"id":"32849491-103-110-3396668","span":{"begin":1335,"end":1338},"obj":"[\"25389405\"]"},{"id":"32849491-229-236-3396669","span":{"begin":1472,"end":1475},"obj":"[\"24337479\"]"},{"id":"32849491-152-159-3396670","span":{"begin":1631,"end":1634},"obj":"[\"24337479\"]"},{"id":"32849491-188-195-3396671","span":{"begin":1900,"end":1903},"obj":"[\"26830879\"]"}],"text":"For the more efficient CSC elimination, different approaches that have been developed can be used, i.e., tandem CAR T-cells (TanCAR) (583) as well as single universal (U) tricistronic transgene CAR T-cells (UCAR T-cells) (584). Multi-targeting of Her2, IL-13 receptor subunit alpha-2 (IL13Rα2), and ephrin-A2 (EphA2) was shown to overcome antigenic heterogeneity in 15 primary GBM samples and to increase the therapeutic success using xenograft models (584). Targeting two or more antigens may increase the risk for on-target/off-tumor toxicity, since most of the antigens are not only expressed on malignant cells, but also on healthy cells (60, 585). Improved safety, specificity, and flexibility can be obtained using universal CARs (UniCAR) or split, universal and programmable (SUPRA) CARs (585–589). Both consist of an inert and universal CAR construct without a single chain variable fragment (scFv) adaptor molecule domain in combination with a multiple tumor-targeting scFv adaptor molecule (585, 588, 589). In both cases, the activity of CAR T-cells can be regulated by the dosage of the scFv adaptor molecules or by introducing competitive molecules, such as leucine zippers as a regulator for the SUPRA CARs (588, 589). Additional safety of CAR T-cells can be achieved by the induction of suicide genes, e.g., iCasp9 (590, 591) or by inhibitory CAR (iCAR) constructs, in which signaling domains consist of an immuno-inhibitory receptor [e.g., CTLA-4 or PD-1; (592)]. An antigen only expressed on the surface of healthy cells is a target of iCAR and therefore the the attack of non-tumorigenic cells is greatly reduced (592). Specificity can be improved by using synthetic Notch (synNotch) receptors. The binding of synNotch specific to the antigen induces the cleavage of an intracellular domain and activates in turn the transcription of a second CAR, specific to another tumor antigen (593)."}

{"project":"MyTest","denotations":[{"id":"32849491-27427982-34971036","span":{"begin":134,"end":137},"obj":"27427982"},{"id":"32849491-29016929-34971037","span":{"begin":222,"end":225},"obj":"29016929"},{"id":"32849491-29016929-34971038","span":{"begin":453,"end":456},"obj":"29016929"},{"id":"32849491-28270302-34971039","span":{"begin":643,"end":645},"obj":"28270302"},{"id":"32849491-30666307-34971040","span":{"begin":647,"end":650},"obj":"30666307"},{"id":"32849491-30666307-34971041","span":{"begin":796,"end":799},"obj":"30666307"},{"id":"32849491-30984613-34971041","span":{"begin":796,"end":799},"obj":"30984613"},{"id":"32849491-31907405-34971041","span":{"begin":796,"end":799},"obj":"31907405"},{"id":"32849491-31091431-34971041","span":{"begin":796,"end":799},"obj":"31091431"},{"id":"32849491-29706540-34971041","span":{"begin":796,"end":799},"obj":"29706540"},{"id":"32849491-30666307-34971042","span":{"begin":1001,"end":1004},"obj":"30666307"},{"id":"32849491-31091431-34971043","span":{"begin":1006,"end":1009},"obj":"31091431"},{"id":"32849491-29706540-34971044","span":{"begin":1011,"end":1014},"obj":"29706540"},{"id":"32849491-31091431-34971045","span":{"begin":1221,"end":1224},"obj":"31091431"},{"id":"32849491-29706540-34971046","span":{"begin":1226,"end":1229},"obj":"29706540"},{"id":"32849491-27138041-34971047","span":{"begin":1330,"end":1333},"obj":"27138041"},{"id":"32849491-25389405-34971048","span":{"begin":1335,"end":1338},"obj":"25389405"},{"id":"32849491-24337479-34971049","span":{"begin":1472,"end":1475},"obj":"24337479"},{"id":"32849491-24337479-34971050","span":{"begin":1631,"end":1634},"obj":"24337479"},{"id":"32849491-26830879-34971051","span":{"begin":1900,"end":1903},"obj":"26830879"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"For the more efficient CSC elimination, different approaches that have been developed can be used, i.e., tandem CAR T-cells (TanCAR) (583) as well as single universal (U) tricistronic transgene CAR T-cells (UCAR T-cells) (584). Multi-targeting of Her2, IL-13 receptor subunit alpha-2 (IL13Rα2), and ephrin-A2 (EphA2) was shown to overcome antigenic heterogeneity in 15 primary GBM samples and to increase the therapeutic success using xenograft models (584). Targeting two or more antigens may increase the risk for on-target/off-tumor toxicity, since most of the antigens are not only expressed on malignant cells, but also on healthy cells (60, 585). Improved safety, specificity, and flexibility can be obtained using universal CARs (UniCAR) or split, universal and programmable (SUPRA) CARs (585–589). Both consist of an inert and universal CAR construct without a single chain variable fragment (scFv) adaptor molecule domain in combination with a multiple tumor-targeting scFv adaptor molecule (585, 588, 589). In both cases, the activity of CAR T-cells can be regulated by the dosage of the scFv adaptor molecules or by introducing competitive molecules, such as leucine zippers as a regulator for the SUPRA CARs (588, 589). Additional safety of CAR T-cells can be achieved by the induction of suicide genes, e.g., iCasp9 (590, 591) or by inhibitory CAR (iCAR) constructs, in which signaling domains consist of an immuno-inhibitory receptor [e.g., CTLA-4 or PD-1; (592)]. An antigen only expressed on the surface of healthy cells is a target of iCAR and therefore the the attack of non-tumorigenic cells is greatly reduced (592). Specificity can be improved by using synthetic Notch (synNotch) receptors. The binding of synNotch specific to the antigen induces the cleavage of an intracellular domain and activates in turn the transcription of a second CAR, specific to another tumor antigen (593)."}

{"project":"2_test","denotations":[{"id":"32849491-27427982-34971036","span":{"begin":134,"end":137},"obj":"27427982"},{"id":"32849491-29016929-34971037","span":{"begin":222,"end":225},"obj":"29016929"},{"id":"32849491-29016929-34971038","span":{"begin":453,"end":456},"obj":"29016929"},{"id":"32849491-28270302-34971039","span":{"begin":643,"end":645},"obj":"28270302"},{"id":"32849491-30666307-34971040","span":{"begin":647,"end":650},"obj":"30666307"},{"id":"32849491-30666307-34971041","span":{"begin":796,"end":799},"obj":"30666307"},{"id":"32849491-30984613-34971041","span":{"begin":796,"end":799},"obj":"30984613"},{"id":"32849491-31907405-34971041","span":{"begin":796,"end":799},"obj":"31907405"},{"id":"32849491-31091431-34971041","span":{"begin":796,"end":799},"obj":"31091431"},{"id":"32849491-29706540-34971041","span":{"begin":796,"end":799},"obj":"29706540"},{"id":"32849491-30666307-34971042","span":{"begin":1001,"end":1004},"obj":"30666307"},{"id":"32849491-31091431-34971043","span":{"begin":1006,"end":1009},"obj":"31091431"},{"id":"32849491-29706540-34971044","span":{"begin":1011,"end":1014},"obj":"29706540"},{"id":"32849491-31091431-34971045","span":{"begin":1221,"end":1224},"obj":"31091431"},{"id":"32849491-29706540-34971046","span":{"begin":1226,"end":1229},"obj":"29706540"},{"id":"32849491-27138041-34971047","span":{"begin":1330,"end":1333},"obj":"27138041"},{"id":"32849491-25389405-34971048","span":{"begin":1335,"end":1338},"obj":"25389405"},{"id":"32849491-24337479-34971049","span":{"begin":1472,"end":1475},"obj":"24337479"},{"id":"32849491-24337479-34971050","span":{"begin":1631,"end":1634},"obj":"24337479"},{"id":"32849491-26830879-34971051","span":{"begin":1900,"end":1903},"obj":"26830879"}],"text":"For the more efficient CSC elimination, different approaches that have been developed can be used, i.e., tandem CAR T-cells (TanCAR) (583) as well as single universal (U) tricistronic transgene CAR T-cells (UCAR T-cells) (584). Multi-targeting of Her2, IL-13 receptor subunit alpha-2 (IL13Rα2), and ephrin-A2 (EphA2) was shown to overcome antigenic heterogeneity in 15 primary GBM samples and to increase the therapeutic success using xenograft models (584). Targeting two or more antigens may increase the risk for on-target/off-tumor toxicity, since most of the antigens are not only expressed on malignant cells, but also on healthy cells (60, 585). Improved safety, specificity, and flexibility can be obtained using universal CARs (UniCAR) or split, universal and programmable (SUPRA) CARs (585–589). Both consist of an inert and universal CAR construct without a single chain variable fragment (scFv) adaptor molecule domain in combination with a multiple tumor-targeting scFv adaptor molecule (585, 588, 589). In both cases, the activity of CAR T-cells can be regulated by the dosage of the scFv adaptor molecules or by introducing competitive molecules, such as leucine zippers as a regulator for the SUPRA CARs (588, 589). Additional safety of CAR T-cells can be achieved by the induction of suicide genes, e.g., iCasp9 (590, 591) or by inhibitory CAR (iCAR) constructs, in which signaling domains consist of an immuno-inhibitory receptor [e.g., CTLA-4 or PD-1; (592)]. An antigen only expressed on the surface of healthy cells is a target of iCAR and therefore the the attack of non-tumorigenic cells is greatly reduced (592). Specificity can be improved by using synthetic Notch (synNotch) receptors. The binding of synNotch specific to the antigen induces the cleavage of an intracellular domain and activates in turn the transcription of a second CAR, specific to another tumor antigen (593)."}