February 19, 2026 – A personalized mRNA vaccine has demonstrated durable immune responses in patients with triple-negative breast cancer (TNBC), offering a potential new avenue for treatment and prevention of recurrence. The findings, stemming from a phase 1 clinical trial, suggest that tailoring vaccines to an individual’s tumor mutations can stimulate a robust and lasting immune response.
The study, conducted in Germany and Sweden, focused on patients who had already undergone standard treatment – typically neoadjuvant chemotherapy followed by surgery, and potentially adjuvant chemotherapy or radiation. Researchers developed individualized vaccines based on the unique neoantigens present in each patient’s tumor. Neoantigens are mutated proteins that are not found in normal cells, making them ideal targets for the immune system.
The trial enrolled 14 patients with invasive adenocarcinoma TNBC who had previously received standard care. Eligibility required that tumors express at least five neoantigens, a key factor in determining the potential for a successful vaccine response. The individualized neoantigen vaccine consisted of two single-stranded RNA molecules, each encoding up to ten neoantigen targets. These RNA molecules were then formulated into a liposomal formulation (RNA–LPX) for intravenous administration.
The process of creating these personalized vaccines was complex. Tumor samples underwent extensive genomic sequencing to identify somatic mutations. These mutations were then used to predict which peptides, or neoantigens, would be most likely to trigger an immune response. The identified neoantigens were incorporated into the mRNA vaccine, essentially instructing the patient’s cells to produce these mutated proteins and alert the immune system.
Researchers assessed the feasibility, safety, and tolerability of the vaccine, as well as its ability to induce antigen-specific immune responses. Long-term follow-up, extending up to three years for 11 patients, revealed sustained T cell immunity. This is a critical finding, as durable immune responses are essential for preventing cancer recurrence.
The study utilized sophisticated techniques to monitor the immune response. Immunogenicity was assessed through Interferon-gamma (IFNγ) ELISpot assays, which measure the ability of T cells to produce IFNγ, a key signaling molecule in the immune response. Researchers also employed peptide-MHC multimer staining to identify and quantify neoantigen-specific CD8+ T cells, a type of immune cell that directly kills cancer cells. Single-cell RNA sequencing was used to further characterize the immune response at a granular level, revealing the diversity and functionality of T cell clones.
Analysis of tumor samples before and after vaccination revealed the presence of neoantigen-specific T cells within the tumor microenvironment, suggesting that the vaccine was able to infiltrate the tumor and mount an attack. Tracking of T cell receptor (TCR) sequences showed that some of the T cell clones generated by the vaccine were present in both the blood and the tumor, indicating a systemic and localized immune response.
The manufacturing process for these individualized vaccines was conducted under good manufacturing practice (GMP) conditions, ensuring quality and safety. While the initial turnaround time for vaccine production wasn’t pre-specified due to the novelty of the process, researchers continuously optimized the manufacturing workflow during the trial.
One patient, P12, underwent particularly detailed analysis, including post-vaccination next-generation sequencing. This analysis revealed changes in gene expression patterns consistent with an activated immune response. Gene set enrichment analysis (GSEA) identified pathways related to immune function that were upregulated after vaccination.
While the study represents a significant step forward, it’s important to note that it was a phase 1 trial, primarily designed to assess safety and feasibility. Larger, randomized controlled trials are needed to confirm the efficacy of this approach and determine its potential to improve clinical outcomes. The combination of this mRNA personalized cancer vaccine with PD-1 monoclonal antibody (Keytruda) has already advanced to Phase 3 clinical trials, marking a significant milestone in the field of cancer immunotherapy. This makes it the first mRNA cancer vaccine to reach this stage of clinical development.
The research highlights the promise of personalized cancer vaccines as a potential new treatment modality. By harnessing the power of the immune system to target unique tumor mutations, these vaccines offer a potentially more effective and less toxic approach to cancer therapy. Further research is ongoing to refine this technology and expand its application to other types of cancer.
