Researchers have now succeeded in creating the rare and important immune cells, plasmacytoid dendritic cells, in a laboratory. This opens for the possibility of using the cells to treat diseases such as cancer and viral infections within the foreseeable future.

2021.10.13 | Line Rønn

A new study from Aarhus University delivers a significant advancement in stem cell research and the opportunities for treating patients with a new cell-based immunotherapy.

As the first in the world, researchers from the Department of Biomedicine have succeeded in finding a stem cell-based method for developing the rare but important immune cells plasmacytoid dendritic cells (pDCs) under the regulations governing Good Manufacturing Practice (GMP).

pDCs play a central and important role in the immune system as they are able to recognise and fight viral infections. Recent research shows that this type of cell probably also plays an important role in relation to cancer, respiratory infections and autoimmune diseases.

For this reason, pDCs have been a sought-after commodity in the research community, and particularly within cell-based immunotherapy, where they have great potential. However, the fact that very few of these special immune cells can be extracted from the blood has hampered progress.

As Professor Martin Roelsgaard Jakobsen and Associate Professor Rasmus Bak explain, the study has exciting perspectives.

"In collaboration between our two research groups, we’ve developed a GMP cultivation method whereby we’re able to generate millions of pDCs by giving blood stem cells the right nutrients and conditions. Our work opens up the possibility of being able to begin treatment with stem cell-derived pDCs for diseases such as cancer and viral infections within the foreseeable future," says Martin Roelsgaard Jakobsen.

"We know that the pDCs have a crucial role to play in how the body fights diseases such as SARS-CoV-2, and with different types of cancer, we can also see that the presence of pDCs in tumours correlates positively with patient-survival, so there are big perspectives," he explains.

Difficult to extract from the blood

There are less than 0.1 per cent of pDCs in the blood – but it is the cell that produces the most interferon, which is an essential part of the body's immune system. In the study, which has just been published in the journal eLife, the researchers show how they are able to utilise this new method for converting a few hundred thousand blood stem cells into more than 500 million pDCs. By comparison, the researchers would have to use 150 litres of blood to extract the same amount of immune cells.

"We have a repertoire of research projects based on the potent method that we’ve just published. Among other things, we are learning more about the properties, mechanisms, and biological roles of pDCs. Our vision is to be able to give a patient these pDCs in the blood, and briefly get a very potent response that fights the disease," says Associate Professor Rasmus Bak.

"We also have research projects investigating how we can utilise new genetic technology tools such as CRISPR/Cas on the immune cells. We expect to be able to make genetic improvements to the functions of pDCs or give them completely new properties," he says.

The ambition is initially to take pDCs generated from the patient's own stem cells which the researchers will use for treatment.

Clinical trials within the foreseeable future

Progress in cell therapy is one of the great hopes for curing serious and chronic diseases.

In their laboratories, Martin Roelsgaard Jakobsen and Rasmus Bak use stem cells from fully anonymised healthy donors, and the pDCs are created in accordance with the regulations for Good Manufacturing Practice (GMP), which makes it possible to use the method therapeutically.

The research groups also expect their research teams to be ready with a cell therapy product that can be clinically tested within a few years.

"Cell therapy is a form of treatment that will have a huge role to play in the future as we improve our understanding of the interaction between our immune cells and diseased tissue. Here we’ve presented a new type of cell therapy with huge and untapped potential. In principle, there are no limitations in relation to which diseases we can use it on," says Professor Martin Roelsgaard Jakobsen.

 

The research results – more information:

• The researchers from Aarhus University have found a way to generate plasmacytoid dendritic cells (pDCs) from haematopoietic stem cells.
• With the help of optimised conditions for the cells combined with the implementation of stem cell pre-expansion, the researchers can generate on average 465 million stem cell-derived pDCs starting from 100,000 blood stem cells.
• The experiment is the first to successfully generate fully functional pDCs from blood stem cells, and this forms the basis for investigating these pDCs for cell-based immunotherapy. Expectations are, that immunotherapy with pDCs is able to initiate an immunological response in the patient, which can help fight e.g. cancer or infections.
• Professor Martin Roelsgaard Jakobsen, Associate Professor Rasmus O. Bak and former Postdoc Anders Laustsen, have together channelled the research over to the newly established company UNIKUM Therapeutics, which has the objective of using pDCs in clinical therapeutic treatment. The young start-up company was founded in 2020, and the company has received a licence for the patent – which is owned by Aarhus University – for the production of pDC-based cell therapy.
• The study is translational research.
• External partners: Researchers at Obstetrics and Gynaecology, Aarhus University Hospital.
• The project is supported by grants to Martin R Jakobsen and Rasmus Bak from the Lundbeck Foundation and the Independent Research Fund Denmark, among others.
• The article is published in the scientific journal eLIFE.

 

Contact:

Professor Martin Roelsgaard Jakobsen

Department of Biomedicine at Aarhus University

mrj@biomed.au.dk

Mobil: +4526153369

 

Associate Professor Rasmus O. Bak

Department of Biomedicine at Aarhus University

bak@biomed.au.dk

Mobil: +4593929100