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Fig. 3 | Journal of Experimental & Clinical Cancer Research

Fig. 3

From: Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies

Fig. 3

Elimination switches. Reversible switches A. The STOP CAR is a dimer of two functional chains that can be disrupted by a Bcl-XL inhibitor. B. Lenalidomide induces CRL4CRBN E3 ubiquitin ligase-mediated ubiquitination and degradation of the hybrid zinc finger degron ZFP91-IKZF3-incorporated CAR. C. Asunaprevir binds to HCV NS3 protease in SWIFF-CAR and inhibits the degradation of the protease/degron complex. Therefore, the whole CAR would be degraded by degron. D. The CAR contains a conditional scFv based on the camelid antibody. MTX binds to the scFv and induces scFv conformational changes, therefore inhibiting CAR from recognizing TAA. Irreversible switches E. Upon the administration of monoclonal antibodies, CAR T-cells expressing CD20 or EGFRt can be irreversibly eliminated through the CDC or ADCC effect. F. The administration of AP1903 induces the dimerization of iCasp9, which triggers downstream apoptotic cascades, resulting in CAR T-cell death. G. When ganciclovir is administered, HSV-TK phosphorylates ganciclovir to form the toxic ganciclovir-triphosphate compound, leading to the inhibition of DNA synthesis and CAR T-cell death. H. T-cells transfected with mRNA transiently encode CAR, the expression of which can be downregulated with mRNA degradation

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