Tetramer Reagents for Monitoring an Immune Response - Isis Project No 1049
Research by Professor Vincenzo Cerundolo at the Institute of Molecular Medicine, University of Oxford has identified a powerful method which can greatly accelerate development of new vaccines by allowing rapid and accurate analysis of human cytotoxic T-lymphocyte (CTL) responses.
Therapeutic areas/application
Development of new vaccines.
Background
In order to develop new vaccines and to test the efficiency of vaccination protocols, it is necessary to accurately, quickly and efficiently test the CTL response that is provoked by the vaccination regimen. Without such testing it is difficult to determine whether the vaccine or vaccination strategy marks an improvement over those that already exist. As an answer to this problem, the Oxford inventors have developed a novel tetramer based technique to directly monitor the CTL population expanded by vaccination.
The Problem
The mouse is often used as an experimental animal to test vaccination strategies. In order to provide a biological environment that is as close as possible to the human environment, transgenic mice with the ability to express human MHC molecules are often used. Mice expressing chimeric MHC in which the alpha1 and alpha2 domains are derived from human and the alpha 3 domain derived from mice have proved particularly useful in this respect. It is possible to monitor CTLs using multimeric MHC molecules displaying peptide/epitope to detect CTLs raised to that epitope. However, the usefulness of MHC multimers is compromised in mouse models since the MHC is usually of human origin whereas the test model is non-human and will therefore have the protein CD8, which does not effectively bind to human MHC.
The Oxford Invention
The Oxford inventors have devised a chimeric multimeric MHC structure that is able to overcome the limitations of using human MHC multimers in non-human test species. These chimeric MHC molecules are more efficient at detecting CTL responses to desired epitopes than non-chimeric structures. The binding of such chimeric MHC structures to CTL is easily detectable by using, for example, fluorescently labelled tetramers. Such chimeric MHC structures can also be used to quickly and efficiently determine epitopes in a particular protein.
Commercialisation Opportunity
This excitingOxford technology is the subject of a patent application. Companies interested in product developments arising from this work are invited to contact Isis Innovation to discuss how they could utilise this technology