Anti-receptor antibodies: Is it better to displace the dummy ligand?

A problem presented at the UK MMSG Loughborough 2008.

Presented by:
Dr Mark Penney (Clinical Pharmacology, AstraZeneca)
GS  Bagri, CJW Breward, LK Dyson, JR King, MS Penney, D Schley, D Villasana, JP Ward, JAD Wattis

Problem Description

Monoclonal antibodies have the potential to be excellent therapeutic proteins; it is possible to optimise the antibody to only bind the designated target, reducing the off-target side effects common to small molecule drugs. The ability to more precisely design the binding of the antibody allows work to be performed determining the optimal mechanism before the antibody is produced.

We would like the Study Group to build a model for a system of a ligand, dummy ligand and signalling and dummy receptor, with an anti-receptor antibody, and considering the turnover of the proteins. We would like the Group to determine whether either mechanism is advantageous and, if so, under what circumstances and how this relates to in vitro measurements of the system.

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Study Group Report

This report describes an investigation into how a drug in the form of an antibody can influence or control a signalling ligand/false ligand/receptor system, in particular, whether it is more advantageous for the antibody to block all ligand access to a receptors or just to prevent the signalling ligand. The system is described as set of chemical reactions, which is modelled using mass action kinetics to derive a system of ODEs. The effectiveness of an antibody is assessed using asymptotic analysis.

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