Next Generation Multimer Staining

Development of Products for the Specific Staining of T Cells for Research and Diagnostics

T cells are specialized cells of the immune system that recognize pathological changes in body cells and that can kill these pathologically changed cells. T cells are therefore in the front line against cancer and viral infections. An activated T cell specific against a certain pathogen or mutation proliferates ("clonal expansion"), which changes the proportion of this T cell and its offspring in the total T cell population. The immune response of a patient can thus be estimated based on the relative proportion of antigen-specific T cells.

The established method of tetramer or multimer staining allows to monitor the number of specific T cells in a T cell population. Here, T cells are labelled with the aid of a specific HLA (human leukocyte antigen)/peptide combination to which a dye is coupled. This enables the monitoring of the course of an immune response or the isolation of T cell clones, for example to strengthen the body's own immune response in cancer patients. These and similar T cell therapies are new approaches in individualized medicine, from which great medical advances are expected.

The central step in multimer staining is the loading of HLA molecules with a specific peptide (pHLA). However, current methods are very inefficient and labor intensive and have to be carried out anew for each peptide. This is a major reason why currently no manufacturer is able to offer an appropriate range of pHLA and current products are quite expensive.

A new patent-pending technology developed at imusyn enables the production of eukaryotic HLA class I that are stabilized by a disulfide bridge. These novel HLA are predestined for peptide loading and multimer staining. Imusyn currently produces about 100 HLA class I and has a much broader range of allotypes than any other commercial multimer staining supplier. In addition, imusyn is in a position to develop its own carrier molecules, in which the degree of multimerization and thus the degree of sensitivity and specificity of the reagent can be controlled.

We therefore decided to develop a next generation multimer staining product. We are happy to announce that the European Regional Development Fund (EFRE) funds the realization of this worldwide unique project.

In order to identify a wider range of T cells and thus to advance the possibilities of individual medicine, within this project we will develop products for the specific staining of T cells that cover the broadest possible range of HLA class I allotypes. In addition to HLA, we intend to develop carrier molecules that allow different degrees of multimerization or that can specifically control them, thus enabling a reversible staining of cells. This is a decisive step towards improved T cell diagnostics and isolation, which might allow for the development of much more targeted therapies, for example in cancer patients.