TCR-Engineered T Cells Targeting Shared β-Catenin Mutation Eradicate Solid Tumors, Earns OUS Research Prize
核心洞察
A study published in Nature Immunology demonstrates that T cells engineered with TCRs from healthy donors can target a shared β-catenin mutation (搜索) to eradicate solid tumors (搜索).
The research, led by PhD candidate Maria Stadheim Eggebø and Professor Johanna Olweus, won the OUS award for outstanding research articles published in fall 2025.
Mutations specific to cancer cells form unique peptides recognized by T-cell receptors, but patients' own T cells often fail to recognize these neoantigens.
A groundbreaking study demonstrating that T cells engineered with T-cell receptors (TCRs) from healthy donors can target a shared β-catenin mutation (搜索) and eradicate solid tumors (搜索) has been recognized with the Oslo University Hospital (搜索) (OUS) award for outstanding research articles. The work, published in Nature Immunology, was led by PhD candidate Maria Stadheim Eggebø and colleagues in Professor Johanna Olweus' group at PRIMA, a Centre of Excellence in precision immunotherapy at the University of Oslo (UiO) and OUS.
The award was presented at Rikshospitalet on June 12, honoring articles published in the fall of 2025 that achieved international impact, demonstrated particularly high quality, and communicated important findings.
Harnessing Mutations as Cancer-Specific Targets
Mutations have proven to be promising targets for cancer treatment because they are specific to cancer cells and not found in healthy cells. These mutations can form unique peptides that are displayed on the surface of cancer cells and can be recognized by T cells via their T-cell receptor. The fundamental challenge, however, is that a patient's own T cells often do not recognize these neoantigens.
"T cells from healthy donors, on the other hand, have been shown to be better at this, and T cells modified to express T-cell receptors are a promising treatment strategy," the researchers note.
This approach builds on a breakthrough from Olweus' group published in Science in 2016, which demonstrated that T cells from healthy blood donors can recognize and kill cancer cells far more effectively than the patient's own T cells. The underlying mechanism relates to how cancer develops: it often grows slowly and silently, and the immune system does not receive the powerful danger signals that accompany acute infections. Over time, the patient's immune system can adapt to the cancer, with T cells becoming exhausted or learning to tolerate the changes from cancer cells.
"These are mechanisms that a healthy blood donor has not been exposed to. Therefore, immune cells from healthy people can be better at recognizing cancer cells. By extracting and copying T cell receptors from healthy donors, we can reprogram the patient's own T cells to recognize the cancer cells better," Olweus explains.
Recognition and Clinical Significance
"It's very exciting that our work has been awarded the OUS article prize! We wish to thank the research committee and the committee for this recognition," said Eggebø.
The study, titled "TCR-engineered T cells targeting a shared β-catenin mutation (搜索) eradicate solid tumors (搜索)," represents a significant advance in the field of precision immunotherapy. The β-catenin mutation is a common mutation found across multiple cancer types, making it an attractive shared target for TCR-based therapies.
Professor Olweus, who was recently awarded the King Olav V's Cancer Research Prize — the largest cancer research prize in Norway — has been at the forefront of efforts to identify the "Achilles heel" of cancer cells. "Cancer cells are 99 percent alike normal cells. We need to find what really distinguishes cancer cells from healthy cells. Then we can target the T cells there," she says.
The research group is now preparing to test their treatment approach in a clinical study at Oslo University Hospital (搜索), with the first patients expected to be included in 2026. The initial goal is to demonstrate that the treatment is safe.
"It is one thing to publish good academic work. A completely different, but at least equally demanding part, is to take a self-developed treatment all the way to the clinic. There was no infrastructure for this in Norway, so we have had to build up a lot ourselves. The fact that we are now on the threshold of testing the treatment on patients is incredibly motivating," Olweus says.
The work underscores the growing potential of TCR-engineered T cell therapies as a strategy for solid tumors (搜索), particularly in lung cancer (搜索) and prostate cancer (搜索), where new immunotherapy approaches are urgently needed for patients who do not benefit adequately from existing treatments.