Maria Ormhøj

Personalised cancer treatment: The cure of the future

Medicine and medico technology Health and diseases Cells Genes and genomes

Postdoc at DTU Health Tech, Maria Ormhøj, works with CAR T-cell cancer therapy with focus on brain tumours.

If we offer personalised treatment to each patient, we can avoid applying a scattergun technique and to a higher degree ensure efficient treatment.

Postdoc Maria Ormhøj is convinced that the cure of the future for several types of cancer may be found in personalized treatment. “The fact that you can customise a specific treatment for a specific patient must be better than offering the same drug to everyone. And we can see that immunotherapy is very efficient when it works.”

Reprogramming the immune system to fight cancer

Immunotherapy is a personalised type of treatment, where the patient’s immune system is reprogrammed to fight the cancer. CAR T-cell therapy, which is a kind of immunotherapy, is currently successfully used to treat leukaemia and other types of haematological cancer in children. In CAR T-cell therapy, a specific gene coding for a receptor to the patient’s T-cells is added. This induces T-cells to be directed towards a given antigen on the surface of the tumour cell. In other words, the T-cells are reprogrammed to recognise specific cancer cells. The idea is that the patient’s immune system is employed to fight the disease.

Maria Ormhøj’s goal is to develop this type of treatment against solid tumours. In her project, which is funded by the Independent Research Fund Denmark, she focuses on Glioblastoma, which is a very aggressive cancer in the brain, where patients in average have a life expectancy of 15 months after their diagnosis. In the long term, she expects that the results will also be transferable to other types of solid tumours.

"The fact that you can customise a specific treatment for a specific patient must be better than offering the same drug to everyone."
Postdoc Maria Ormhøj

“T-cells are the immune system’s elite soldiers, and they are efficient at killing infected cell. We exploit this knowledge to kill cancer cells. Specifically, we wrap CAR DNA in a modified HIV particle benefitting from its natural ability to infect cells. This way, we can deliver the CAR gene to the T-cells, enabling them to express this new receptor that allows them to localize and kill cancer cells”, Maria Ormhøj explains.

Solid tumours are challenging

Today, the CAR T treatment has little to no effect on solid tumours. The challenge is that it is difficult to find an antigen on the tumour surface to direct the T-cells towards. And because a lot of the tumour consists of our own tissue, healthy tissue will be at risk of being targeted. Additionally, solid tumours are very heterogeneous in their “antigen” composition, among other things due to the way they mutate. Therefore, only parts of the tumour will be killed, and it will be difficult to remove the whole tumour.

”We will use and develop these CAR T-cells further to achieve a secondary immune response in the patient, and thus get a much broader immune response against several kinds of tumour cells. We hope such an approach will improve the efficiency of the therapy. The current status is that we have created a great library of different CAR T-cells, set up a good collaboration with researchers at Lund University, who have excellent models based on tumours from glioblastoma patients, and we have set up our own viral system at DTU for the production of these cells”, says Maria Ormhøj, who initiated her project in the beginning of 2021.

The current CAR T-cell therapy is further challenged by the fact that it takes place ex vivo, i.e., outside the body. Cells are taken out of the patient, frozen and sent for genetic reprogramming to for example a company like Novartis, where the cells are thawed, reprogrammed, frozen, and returned to the patient. It is a prolonged and not least very expensive process that typically takes a month or longer and costs several hundreds of thousands USD for just one infusion.

More research on the way

Maria Ormhøj’s project is part of a larger focus on the CAR T-cell area at DTU Health Tech, which also includes a newly established research center funded by the Novo Nordisk Foundation called NICE - Center for Nano-Immune Cell-Engineering. Maria, who is also involved in the center, elaborates:

”Our hope is to establish a method, where we have nanoparticles delivering the CAR gene in vivo, i.e., directly inside the body. Imagine a new form of personalized therapy, where you have a range of different nanoparticles on the shelf, and you can give the patient a shot of the nanoparticles that contains the CAR genes that match the antigens on exactly their tumour. This way we can customise a fast, cheap and more efficient CAR T-cell therapy to each patient.”

She continues, ”It is unsustainable to carry out CAR T-cell therapy ex vivo as we do it today. If we can develop a much cheaper treatment, it will benefit many more patients. And that is exactly the point – to help patients. That’s our goal.”

CAR T-cells

Caption: CAR T-cells culture in the lab at DTU Health Tech. (Photographer: Jesper Scheel)

Top photo: Postdoc Maria Ormhøj (Photographer: Jesper Scheel)

 

Facts

CAR T-cell therapy

A type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer. (Source: cancer.gov)

 

About the NICE center

The new Center for Nano-Immune Cell-Engineering (NICE) will be headed by Professor Sine Reker Hadrup, and it will run for 6 years.

The project includes three partners:

  • Professor Sine Reker Hadrup will lead the center and contribute with her extensive knowledge in immunology and cancer-immunotherapy.
  • Associate Professor Yi Sun will contribute with her great experience in creating advanced nanomaterials with novel structures and functionalities.
  • Professor Hinrich Abken from University Hospital Regensburg will contribute with his well-known work in evolutionary design of CAR genes and transposon systems.

Read more: Novo Challenge grant for interdisciplinary research center