Many types of cancer arise due to errors, or mutations, in our genetic material. These mutations lead to changes in our genes that assist cancer in growing and spreading within the body.?
Such mutations are usually unique from patient to patient. As a result, there has been significant investment in cancer treatments tailored to each individual patient and their unique cancer disease.?
However, there are also errors or mutations that are common across different cancer types. These so-called "public mutations" are found in multiple patients, not just one individual.
“A treatment targeting such a common mutation could be used for many more patients, not just the individual,” says Johanna Olweus, a professor at the University of Oslo and group leader at Oslo University Hospital.
Olweus and her Norwegian colleagues have now developed a new type of immunotherapy. The treatment has proven to be highly effective in targeting cancers with such common mutations.
“Our findings give hope that we can develop treatments for cancer patients who currently have no good treatment options available,” says Olweus.
The study's findings were published in the prestigious journal Nature Immunology.
A mutation found in thousands of cancer cases
The mutation they studied is called CTNNB1S37F. It is a specific mutation that causes cancer cells to grow uncontrollably in the body.?
This mutation appears in thousands of cancer cases each year among patients with lung cancer, prostate cancer, and endometrial cancer. These cancer types develop solid tumors in organs or tissues, in contrast to blood cancer.
“This mutation is a notorious driver of tumor growth. However, it is very challenging to target with conventional cancer treatments such as chemotherapy and radiation,” Olweus explains.
Immunotherapy requires recognizable targets for attack
Immunotherapy is a treatment that activates T cells, the body’s own immune defense, to attack cancer. For immunotherapy to be effective, it is necessary for T-cells to recognize targets that allow them to attack cancer cells, such as proteins altered by mutations.
Solid tumors that have metastasized can rarely be cured with conventional cancer treatment. Therefore, many researchers have tried to target T cells in the immune system against mutations in cancer cells. However, this has proven to be difficult.
“First, it is challenging to find mutations that are common to many patients. Secondly, only a small fraction of mutations alter proteins that are presented on the surface of cancer cells,” Olweus explains.
The visibility of these proteins on the cell surface is essential for T cells to recognize them.
“It has also been difficult to find T cells that can recognize the mutated or altered proteins. This is crucial for being able to target the patient's own T cells against the mutation,” she explains.
Reprogramming t cells to recognize and kill cancer cells
Therefore, Olweus and her colleagues first needed to find a target for the treatment. They identified proteins on the surface of cancer cells that were altered due to the mutation. Then, they used T cells from healthy blood donors to find rare T cells capable of recognizing the altered protein.
They transferred properties from the healthy T cells, which could recognize the altered protein, to other T cells. In other words, “reprogrammed” T cells in the laboratory. The programmed T cells were now able to attack and kill cancer cells with the target mutation.
In treating a patient, this kind of programming means inserting a gene into the patient’s own T cells in the laboratory.
“We can thus modify the T cells from patients. This enables them to recognize, seek out, and kill cancer cells with this mutation while leaving normal, healthy cells unharmed since the mutation is only present in the cancer cells,” says Maria Stadheim Eggeb?, a PhD student in the group.
Programmed t cells were highly effective in killing tumors
The researchers tested the programmed T cells on tumors in models created using patient tissue. They also tested the treatment on mouse models with tumors derived from patients. In both cases, they found that T cells effectively killed the cancer cells.
“This is the first time scientists have managed to completely remove solid tumors that come directly from patients by treatment with T cells that are programmed to attack a mutation,” reports researcher Morten Milek Nielsen. “We observed this in cell culture as well as in mouse models transplanted with patient tumors,” he emphasizes.
Targeting the mutation with precision
This discovery is an exciting breakthrough because it may represent a new way to treat tumors.
“What makes our approach unique is that we target a mutation that is critical for the cancer’s survival and spread. We do this with both precision and very high efficiency,” says Olweus. “This is a targeted attack on cancer cells that allows healthy cells to remain unharmed,” she points out.
A breakthrough for patients with lung and prostate cancer
These findings represent a significant advancement in immunotherapy for cancer. Because this mutation is present in many patients, this treatment has the potential to help extensive groups of patients.
“With so many thousands of cases every year, this mutation is an important target for cancer treatment. We hope this will pave the way for future therapies that can help many,” says Eggeb?.
The researchers plan to conduct clinical studies to test the safety and effectiveness of the new immunotherapy moving forward.
“If this proves to be safe and effective, we could be on the brink of a breakthrough for patients with hard-to-treat cancers for which we currently lack effective treatments,” concludes Olweus.
The project has been led by Johanna Olweus and her research group in collaboration with Fridtjof Lund-Johansen’s research group; both are partners in PRIMA, a Centre of Excellence at the University of Oslo and Oslo University Hospital.
Reference
- Eggeb?, M. S. et al. TCR-engineered T cells targeting a shared β-catenin mutation eradicate solid tumors. 2025. Nat. Immunol. https://doi.org/10.1038/s41590-025-02252-1
- Summary of the study in Nature Immunology: Nature Research Briefing https://www.nature.com/articles/s41590-025-02287-4?