Early BioNTech mRNA breast cancer trial delivers surprise in longtime disease control

Triple-negative breast cancer is regarded as one of the most aggressive forms of the disease. Because tumour cells lack the ER, PR and HER2 receptors, many targeted therapies are ineffective. Relapses are common and often occur within the first three years after diagnosis. This has fuelled strong interest in individualised immunotherapies. To date, mRNA approaches in oncology have delivered mixed results, frequently lacking clear evidence of meaningful clinical efficacy.

mRNA-neoantigen strategy delivers disease control

The new Phase I study, led by Marcus Schmidt at the University Medical Centre Mainz in collaboration with BioNTech and published in Nature, provides notable findings. In this small, clearly exploratory trial, 14 patients with early-stage TNBC received a personalised mRNA vaccine following surgery and (neo)adjuvant therapy. Each vaccine encoded up to 20 tumour-specific neoantigens, packaged in lipid nanoparticles and administered intravenously to target dendritic cells.

Neoantigens are molecular features that distinguish cancer cells from healthy tissue. They often become visible to the immune system only when tumour cells are destroyed – something that may occur during (neo)adjuvant treatment. Encoding these neoantigens in an mRNA construct can significantly enhance their immunological visibility.

What makes the study striking is not its size, but the immune response observed. All patients developed vaccine-induced T-cell responses against multiple encoded neoantigens. The induced CD8+ T cells reached frequencies more commonly associated with adoptive T-cell therapies and remained functionally active for years without booster vaccinations. Eleven of the 14 participants remained relapse-free for up to six years, a particularly noteworthy outcome in this aggressive cancer subtype.

Treatment insights point towards combination strategies

The three relapses also yielded important lessons. One patient with a comparatively weak vaccine-induced response achieved complete remission after subsequent anti-PD-1 therapy, suggesting a potential response threshold and supporting combination strategies. Another patient exhibited near-complete loss of MHC class I expression, a known immune escape mechanism that highlights the need for approaches restoring antigen presentation. In a third case, relapse originated from a genetically independent contralateral tumour, underlining the importance of comprehensive tumour sequencing, especially in hereditary settings.

It remains too early for definitive clinical conclusions. As a Phase I study, the primary focus was feasibility and immunogenicity rather than proof of efficacy. Nevertheless, the data suggest that personalised neoantigen mRNA vaccines may generate durable, functional immunity even in biologically aggressive tumours.

According to a company spokesperson, similar immune signals have been observed in other indications, referencing additional publications in Nature in 2023 and 2025 on neoantigen RNA vaccines in pancreatic and other advanced solid tumours.

Several ongoing Phase II trials are now evaluating this approach across different indications, aiming to establish definitive proof of concept against the standard of care. Within BioNTech’s three-pillar strategy, mRNA thus remains a central component. The broader platform concept of personalised cancer vaccination appears to be regaining momentum, extending beyond high-profile indications such as melanoma.