An Asymptotic Analysis of Bivalent Monoclonal Antibody-Antigen Binding

TL;DR

This paper provides an asymptotic analysis of a model describing bivalent antibody-antigen binding, revealing how different conditions affect binding dynamics, which can inform the optimization of monoclonal antibody therapies.

Contribution

It introduces asymptotic approximations for the complex bivalent antibody-antigen binding model, enhancing understanding of its dynamics across different timescales and conditions.

Findings

Different dynamics in antigen-rich and antigen-scarce scenarios

Asymptotic approximations match numerical simulations well

Long-term binding quantities can be estimated for experimental use

Abstract

Ligand-receptor interactions are fundamental to many biological processes. For example in antibody-based immunotherapies, the dynamics of an antibody binding with its target antigen directly influence the potency and efficacy of monoclonal antibody (mAb) therapies. In this paper, we present an asymptotic analysis of an ordinary differential equation (ODE) model of bivalent antibody-antigen binding in the context of mAb cancer therapies, highlighting the added complexity associated with bivalency of the antibody. To understand what drives the complex temporal dynamics of bivalent antibody-antigen binding, we construct asymptotic approximations to the model's solutions at different timescales and antibody concentrations that are in good agreement with numerical simulations of the full model. We show how the dynamics differ between two scenarios; a region where unbound antigens are abundant, and one where the number of unbound antigens is small such that the dominant balance within the model equations changes. Of particular importance to the potency and efficacy of mAb treatments are the values of quantities such as antigen occupancy and bound antibody number. We use the results of our asymptotic analysis to approximate the long-time values of these quantities that could be combined with experimental data to facilitate parameter estimation.