Better tools, better cancer immunotherapy

12 Aug 2019

In the journal Science Immunology, researchers from DTU Health Technology and Jacobs University in Bremen have just published their cutting-edge research demonstrating advancement in detection of a certain type of immune cells, called T cells.

Improved detection of T cells have several therapeutic implications.

For example, in cancer immunotherapy (a therapeutic approach that engage patients own immune cells) characterisation of T cells that recognise cancer cells is crucial for tailoring personalised treatment strategies.

T cells are white blood cells of the immune system that have amazing properties: they can detect cancer cells and virus-infected cells in the body, and they even attack and eliminate these.

This is why T cells constitute an essential part of the immune response, which patients mount, against tumours and viruses.

When applying immunotherapy an immune response against a tumour takes place, the tumour-fighting T cells in the blood of the patient multiply.

To find out how well the immunotherapy is working, scientists and doctors want to check how many tumour-specific T cells a patient has mounted.

The tumour-specific T cells are identified by their specific T cell receptor using a coloured reagent called an MHC tetramer.

Using this reagent, the tumour-specific T cells become visible and can be counted under the microscope or in a high-throughput machine called a flow cytometer.

Super-stable molecule

The MHC proteins of the MHC tetramer reagent were previously difficult to produce due to the inherent instability of the MHC protein, and that used to be a bottleneck in research and diagnosis.

"Whenever a researcher needed MHC tetramers, they had to ask a company to make them, and the process took four to six weeks", explained Prof Sebastian Springer, Jacobs University Bremen.

"Of course, that created big problems if they had a sick patient they wanted to diagnose, or if they were following a really urgent scientific project. The problem was that every MHC protein contains a little piece of a tumour or virus called a peptide, which varies from one patient to the other, and without the peptide, the MHC protein was unstable and perished quickly, even if it was kept in the fridge, thereby destroying the MHC tetramer," added Prof Springer.

With the new invention, MHC molecules can be loaded with peptides instantly, on demand.

"The technology opens a range of new possibilities for tracking disease relevant T cells in patients and to manipulate T cells to specifically fight e.g. cancer" said Sine Reker Hadrup.

Source: Technical University of Denmark

Image credit: Technical University of Denmark