Fig. 1. Types of universal CARs. А. A modular CAR T-cell system with biotin-binding immunoreceptors. B. A modular CAR T-cell system with fluorescein isothiocyanate. C. A modular CAR T-cell system with neoepitopes (5B9, PNE). D. A modular CAR T-cell system with a leucine zipper motif (SUPRA CAR)

Fig. 2. A schematic showing modulation of antitumor activity of CAR T cells in the immunosuppressive tumor microenvironment. A. Silencing the expression of the pdcd-1 gene in T lymphocytes by transfecting them with siRNA. The PD-1 receptor interacts with its ligands PD-L1/2 and inhibits the activating CAR signal. After transfection, siRNA duplexes interact with the RISC-binding complex (RNA-induced silencing complex); one of RNA strands is removed from the complex, whereas the other remains within RISC, binds to mRNA and initiates its degradation. This leads to a decline in the PD-1 expression on the cell surface. B. Knockout of the pdcd-1 gene performed using CRISPR/Cas9 technology. C. TRUCKs: apart from CAR, a plasmid is introduced into the T cell, containing a NFAT responsive element (NFAT-RE) and sequences of genes coding for IL12, IL15 or IL18. The T cell is activated following the interaction between the CAR and the target antigen. This leads to dephosphorylation of NFAT transcription factor that relocates to the nucleus and triggers cytokine production by binding to NFAR-RE. Local secretion of the cytokine initiates immune response against cancer cells invisible for CAR T lymphocytes