SDU researcher Maria Ormhøj wants cancer cells to explode like bombs

- Immunotherapy has set new standards in the treatment of blood cancers, but its success has lagged when it comes to solid tumours such as colorectal cancer. We intend to change that.

These are the words of Maria Ormhøj, assistant professor at the Section for Biotechnology at the Department of Green Technology, Faculty of Engineering (SDU).

With funding from the Independent Research Fund Denmark’s Inge Lehmann programme, she will develop a new generation of so-called CAR T cells. Whereas current treatments often fall short against the tumour’s defence mechanisms, Ormhøj’s strategy is radically different: cancer cells should not merely die – they should make noise when they do.

From a quiet death to an explosion

The challenge with solid tumours is that they consist of many different cell types. Current CAR T-cell therapy is designed to target one specific antigen, often leaving behind a population of cancer cells that the treatment overlooks.

In addition, cancer cells typically die through apoptosis – a “tidy,” silent form of cell death that fails to alert the rest of the body.

Ormhøj’s project aims to reprogram T cells to deliver a specific protein into cancer cells, causing their membranes to rupture and triggering inflammation.

- If we kill a cancer cell the way we do now, it’s a ‘silent’ death that doesn’t really wake up the immune system, Ormhøj explains. She elaborates on her new method with a metaphor:

- Our idea is that if we can kill the cells differently so they essentially burst like tiny bombs, they release a lot of danger signals. That alarms the other immune cells in the body and draws them to the tumour, where they can begin to attack it.

Hacking cells from the inside

Technically, the project lies at the intersection of immunology and biotechnology. Ormhøj describes the process as “hijacking” the cells to deliver proteins they would not typically handle.

By creating a strong inflammatory response within the tumour, the hope is to trigger a domino effect in which the patient’s own immune system learns to recognise and attack the entire tumour – including the parts not initially targeted by the therapy.

- The dream scenario is to prime the endogenous immune response so we can actually make these solid tumours disappear, offering a new potentially curative treatment to patients who are currently incurable, she says.

She points out that in blood cancers, CAR T therapy achieves cure rates of 50–60 per cent, and her ambition is to transfer that success to patients with solid tumours, who today have minimal treatment options and for whom CAR T therapy is currently ineffective.

 

A crucial career milestone

The Inge Lehmann grant—designed to promote gender equality and talent development in Danish research—marks an essential step in Maria Ormhøj’s career. The funding allows her to hire a PhD student and establish herself as an independent research leader.

- It truly builds a bridge—it helps you establish yourself, your name, and a platform you can stand on as an independent researcher, she says.

The project is firmly rooted in international collaboration. The grant will fund research stays with partners in Australia—world leaders in the study of cell death—and in Germany, experts in cancer research using mouse models.

The goal for the coming years is clear: to generate sufficient data to demonstrate that the method is effective, allowing it to be eventually tested in clinical trials involving patients.