Figure 1.
Selection and in vitro characterization of functional CD146.CARCIK cells. (A) Schematic diagram of CD146.CAR structure, including VL and VH domains of single chain fragment variable (scFv), the spacer sequences: CH2mutCH3 (Long), CH3 (Medium) and CD8stalk (Short), the CD28-OX40 co-stimulatory domains and CD3ζ signaling domain. (B) Percentage of expression of CD146.CAR molecules by CIK cells at day21 of culture, determined by FACS analysis (n=2). (C) Short-term cytotoxicity of untransduced (NT) and CD146.CAR CIK cells co-cultured with CD146+ adherent cell line (TIME) at effector:target (E:T) 5:1 ratio (n=3). (D) Cytokines production (IFN-γ and IL-2) by CD146.CAR CIK cells when engaged with TIME cells. IFN-γ and IL-2 were detected by intracellular staining after 5-hours co-culture at 1:3 E:T ratio(n=3). (E) Proliferation determined by intracellular Ki-67 staining of NT and CD146.CAR CIK cells after co-culture with TIME cells for 72 hours at 1:1 E:T ratio (n=3). (*P<0.05, **P<0.01, Two-way ANOVA analysis with Benjamini and Hochberg’s multiple comparisons test).