Figure 7.

Summarized representation of the proposed four key factors contributing interdependently to the optimal design of an anti-idiotypic mask: two define the effective masking of an antibody to avoid on-target off-tumor effects, and two others influence the effective activation of the masked antibody upon proteolytic cleavage.

Figure 7 Alt. text: Schematic showing on the left side the two parameters dictating effective masking (1. Paratope coverage: The more extensively the masks occlude the CDRs involved in antigen binding, the more effective the mask will be. 2. k_on: the higher the mask’s k_on, the less opportunity the antigen has to bind to the antibody while masked), and on the right side, the two parameters dictating effective unmasking (3. k_off and K_D: The mask’s k_off and K_D must be higher than those of the antigen in order to facilitate mask dissociation and competition in binding when the linker is cleaved; 4. Extent of disruption: The closer the mask’s affinity/k_off to the antigen, the larger the disruption required to fully unmask the antibody (additional linker between domains of the mask))