Figure 4. Discontinuous regions consisting of 286-306 combined with 339-378 impart direct cytotoxicity and enhanced avidity, whilst maintaining immune effector functions.
Significantly increased PI uptake (A) and proliferation inhibition (B) by SD339-378 compared to 88hIgG1 on HCT15. Significantly reduced proliferation inhibition by SD307-345 compared to SD286-345, suggesting a contribution by SD286-306 (C). Significantly increased proliferation inhibition by the combination of SD286-306+339-378 compared to 88hIgG1 on HCT15 (D) and COLO205 (E), as well as PI uptake on COLO205 (F). Significantly increased avidity (SPR) by SD339-378 as well as SD286-306+339-378 compared to 88hIgG1 (G). Maintenance of CDC activity on HCT15 (H) and ADCC on COLO205 (I) by SD339-378 as well as SD286-306+339-378 compared to 88hIgG1. Significance versus respective parental constructs was deduced from two-way ANOVA (direct cytotoxicity) or one-way ANOVA with Dunnett’s corrections for multiple comparisons(avidity, and effector functions).