Immune system T cells to be trained to remove cancer

The immune system is an extremely complex organ system capable of fighting disease. However, it can also create disease because immune cells may—so to speak—run riot and start attacking the healthy cells of the body. This very delicate balance has always fascinated Professor Sine Reker Hadrup, and she has embarked on a lifelong journey towards an ever deeper understanding of this vital defence system.

The journey will probably never end, because every time she has understood something, she finds a new level of details. But that only makes her even more curious and keen to exploit her knowledge. During her career spanning 18 years, she has also contributed significantly to the understanding of complex immunological mechanisms. And she has been very actively involved in the development of the special cancer treatment known as immunotherapy, where—instead of injection of cytocides—the body’s own immune system is used to fight cancer cells.

Barcodes

If you want to boost the immune system, the T cells in the blood are a good place to start. They can be described as the elite soldiers of the body; but—when facing cancer cells—they are often defeated because the deviant cells manage to hide, so that they are not killed and removed like viruses and harmful bacteria usually are.

The T cells consequently need help, but—to make them stronger—you must first be able to identify them and understand how they read cancer cells. And how can that possibly be achieved? This question was discussed in depth at a conference Sine Reker Hadrup attended back in 2014. And an idea came to her during these discussions: Perhaps the individual T cell and its special attacking pattern could be marked with some kind of barcode.

She tried out the idea back home in the laboratory at DTU, where she was already well in the process of creating a platform for producing artificial cell surfaces in different variations.

“We developed a technological platform that helps us read what the T cells see and react to. We get living cells from our collaborators—cells from, for example, a cancer node—or blood from cancer patients. On the platform, we mix our reagents with the immune cells, and—using the barcode system we’ve developed—we can then read the interaction between cancer cells and immune cells, for example in connection with a given treatment,” she says.

Special tools for sale

Other researchers can also benefit from both the analysis tool and the reagents developed in Sine Reker Hadrup’s lab for analysis of T-cell reactions. They are sold through the companies ImmuMap and Tetramer Shop, founded by Sine Reker Hadrup together with some of her good colleagues.

“It’s a small niche, and there’s no big profit involved in any of it. I’m not driven by money anyway, but by the desire to see technology applied in the real world to the benefit of people. And it’s very inspiring to be able to contribute something—for example in relation to cancer treatment—where you can really see that there’s a need,” she says.

This is also the driving force behind her latest company, PokeAcell, which she founded with her sister, Anne Reker Cordt, in early spring 2020.

“The name PokeAcell may be a bit too imaginative, but it describes quite well what it’s about,” says Sine Reker Hadrup.

“A Pokémon is a creature trained by a human being, and ‘poke’ means to push. With our technology, we will use a blood test to find the most suitable of the patient’s own T cells, develop them to fight the cancer cells, and then send them back into the body as a kind of specially trained elite soldiers.”

So far, the technology has proved highly effective in the laboratory, and funds have been raised for the first clinical trial in a small group of patients in collaboration with Herlev Hospital. But Sine Reker Hadrup is very humble about the task at hand and knows that there is a long way to go before she hopefully has a completely developed and approved drug:

“It’s fascinating how finely regulated our body is, and it makes it hard to develop drugs. There’s nearly always a derived effect,” she says.

Miracle cure?

Immunotherapy almost sounds like a miracle cure for cancer because it uses the body’s own defence mechanisms and does not involve toxic medication. But it can also have undesired side effects, especially in the form of the immune system being overactivated and ending up attacking the healthy organs of the body. This can, for example, trigger autoimmune diseases such as diabetes.

Furthermore, the method does not work equally well on all cancer types. So far, it has proved most effective in cancers with high levels of mutations, such as melanoma and lung cancer. And it is precisely with melanoma and the rarer form of skin cancer—Merkel cell carcinoma—that PokeAcell starts.

Here, the drug may have a major impact, as around half of the patients do not benefit from the treatment currently available. But Sine Reker Hadrup hopes that it can eventually also be developed into a treatment option for other cancers.

Concurrently with the work in her new company, she is undauntedly continuing her journey into the complex ways of the immune system.

“In many ways, it’s an adventurous journey, although I’m aware that I will probably never reach a final destination. Nor is it likely that we will ever find a single miracle cure for cancer. But—in ten years from now—I think that we will be able to treat most cancer patients with some form of immunotherapy as an important supplement to the current therapies; chemotherapy, radiation, and surgery. We’re slowly moving towards turning cancer into a chronic disease you will be able to live with for a long time,” says the immunology professor optimistically.