Innovative Immunotherapy Targets Common Cancer Mutation, Brings New Hope for Lung and Prostate Cancer Patients

Researchers from the University of Oslo and Oslo University Hospital have developed a groundbreaking immunotherapy approach that specifically targets a common mutation in the CTNNB1 gene, linked to aggressive cancers such as lung and prostate cancer. This novel therapy involves engineering T cells to recognize and attack tumor cells carrying the mutation, showing promising results in preclinical studies. The team successfully eliminated tumors in animal models and patient-derived organoids, demonstrating the potential for this treatment to benefit thousands of patients worldwide.

Cancer often arises from genetic mutations, some of which are shared among many patients, known as "public driver mutations." The CTNNB1S37F mutation affects over 7,000 new cancer cases annually in the U.S. alone and is found in diverse solid tumors. Traditional drugs struggle to target this mutation effectively, but immunotherapy offers a new avenue.

The researchers identified rare T cells in healthy donors capable of recognizing peptides derived from the mutated CTNNB1 protein when presented by common HLA molecules. They then engineered human T cells with receptors for these peptides, enabling targeted destruction of cancer cells with minimal risk to normal tissues.

In tests against mini tumors derived from patient tissues and in mouse models with human tumors, the modified T cells successfully eradicated cancer cells, leading to complete tumor clearance in some cases. This success illustrates that such TCR-based therapies can focus on shared mutations, broadening treatment impact.

The approach differs from previous strategies that targeted broader pathways, which often caused significant side effects. Focusing directly on the mutation ensures precise and safe targeting.

Looking ahead, the team intends to develop similar TCR therapies targeting additional common mutations, aiming to expand treatment options and reduce tumor escape. Their work marks a significant advancement in solid tumor immunotherapy, with the potential to transform cancer treatment for many patients.