FIGURE 2.
Simulated relationship between tissue fluid turnover and TNF-α suppression by three anti-TNF-α biologics. Simulation was performed using binding constants of each biologic to soluble TNF-a at their therapeutic doses. (A) For tissues with low fluid turnover, stable binders are favored but high affinity could contribute to accumulation of antibody-target complex; for tissues with high fluid turnover, fast binders are generally favored but lowering koff beyond fluid turnover rate produces a plateau effect (i.e., affinity ceiling). (B) Summary of 27 licensed antibodies (Li et al., 2018) that bind soluble ligands for treatment of various diseases. Four scenarios proposed based on target binding affinity and tissue fluid turnover rate.