Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors
Fig 6
Simulations of monovalent BS1 binding over varying initial antibody and receptor concentrations.
In these simulations, although the cells express both receptors, the formation of ternary complexes was suppressed by setting kon,6R* and kon,8R*to 0. IL-6R and IL-8R are present in a 1:1 ratio, and simulations were performed for 24 hours after antibody dosing. Similar results for the combination of the monospecific antibodies tocilizumab and 10H2 are included in the Supporting Information (S11 Fig). A, Fraction of total BS1 that is free (unbound) for different levels of receptor expression and initial BS1 concentration. B, Fraction of total receptor concentration (IL-6R + IL-8R) that is unbound (free) or bound (in binary antibody-receptor complexes) for different levels of receptor expression and initial BS1 concentration. The same results, but with antibody and receptor visualization reversed, are included in the Supporting Information (S10 Fig). C, Bound receptor fraction across different initial BS1 and receptor levels. The color indicates the fraction of the total receptor (IL-6R + IL-8R) that is bound to antibody. D, Comparison of monovalent and bivalent binding. The lines indicate the fraction of total receptor (IL-6R + IL-8R) that is bound in different complex types in the original simulations and the simulations restricted to monovalent binding only. Each panel represents a different receptor level (in # receptors/cell).