Danish Researchers: We’re able to mass-produce a rare, key immune cell

Two researchers from the Department of Biomedicine at Aarhus University have made a discovery that could hold promising potentials within immunotherapy:

They have developed a special culturing technique enabling mass production of a rare type of immune cell occurring naturally in human blood.

The discovery has just been published in the eLIFE science journal.

These immune cells, pDCs, hold huge potential for the development of new immunotherapies for treating cancer and life-threatening viral infections.

The problem, however, is the difficulty of obtaining enough pDCs because they only make up about 0.1 percent of our blood.

“And that’s exactly where our method comes into the picture. In the eLIFE article, we demonstrate that the culturing method can be used for generating large amounts of fully functional pDCs in the laboratory. Many investigators have attempted this, but we are the first to succeed”, explain the two researchers, Professor Martin Roelsgaard Jakobsen and Associate Professor Rasmus O. Bak, both Lundbeck Foundation Fellows.

Aiding the body’s defences

But what do pDCs do for our immune response – and what makes them so promising for researchers seeking to develop new immunotherapies?

They have several important functions, explains Bak:

“Firstly, they help to ensure that the human immune system works effectively to combat viruses and infections. This is because the pDCs are large-scale producers of the substance interferon, which plays a key role in the immune response”.

As for the pDCs’ potential in aiding the body’s defences against disease, “we know that they play a key role in SARS-CoV-2, for example”, says Jakobsen: “And in various types of cancer, we can see that the presence of many pDCs in a tumour improves the patient’s chances of survival. So the potential for using pDCs for a wide range of therapies is highly promising”, he stresses.

Ramping up production!

One key element in the cell culture method developed by Jakobsen and Bak is a growth medium of proteins already occurring in the human body, with the addition of synthetic molecules plus a dash of vitamin C.

The growth medium is used to stimulate human blood stem cells, i.e. the special cells that make all the components in our blood, to ramp up pDC production.Associate Professor Rasmus O. Bak

Achieving that was no easy task, but after a large number of experiments and adjustments, they succeeded, explains Bak:

“Basically, the growth medium gets the blood stem cells to produce far more pDCs than they are biologically programmed to”.

And the method really makes it possible to initiate mass production of these coveted immune cells, as demonstrated by the scientific article:

Because with the aid of the growth medium, they can get a few hundreds of thousands of blood stem cells to generate more than 500 million pDCs.

These figures may not be that telling in themselves, but harvesting the same high yield of pDCs from human blood would require a form of ‘filtration’ of at least 150 litres of blood!

“Meaning that we can vouch for the effectiveness of the method – this is mass production” emphasises Jakobsen.

Novel therapies

The two Danish researchers have now embarked on a number of laboratory experiments that will ultimately pave the way for clinical trialling of pDCs, meaning studies in which patients are treated with the immune cells.

Although Jakobsen and Bak are unable to predict when such clinical studies could get underway, they assert that it will be within a “foreseeable” number of years.

The initial idea is to take stem cells from a cancer patient, for example, and then by means of the growth medium stimulate those cells to produce the desired number of pDCs.

This will be done in a pharmaceutical laboratory with strict rules regarding hygiene and quality, and the patients will then have these immune cells injected into their blood. This will fire up their immune response no end with self-produced immune cells, Bak explains: “The idea is to get the immune response to mount a frontal assault against all the diseased cells”.

Finally, the researchers are considering how CRISPR/Cas genetic engineering could modify the immune cells so as to boost their natural disease-fighting ability.

“We’re already onto that”, they say.
 

Facts

• The abbreviation pDC stands for: plasmacytoid dendritic cells.

• The human blood stem cells used by the researchers with the aid of the growth medium to mass produce pDCs came from anonymous donors.

• The two scientists envisage that immunotherapy based on pDC immune cells will ultimately aid treatment of a wide range of diseases, including autoimmune conditions like rheumatoid arthritis.

• In addition to the Lundbeck Foundation, other funding bodies supporting the research project by Rasmus O. Bak and Martin Roelsgaard Jakobsen include the Danish Council for Independent Research.