Individualized mRNA vaccine triggers lasting T cell immunity in breast cancer patients

An mRNA vaccine triggered lasting immune responses in breast cancer patients

Researchers have developed an individualized mRNA vaccine for triple-negative breast cancer (TNBC) that successfully triggered potent, long-lasting immune responses in patients. The vaccine, tested in 14 patients after surgery and standard therapy, induced T cells that remained functional for several years.

In nearly all patients, the vaccine generated high-magnitude T cell responses to multiple tumor-specific neoantigens. These were mostly de novo responses, meaning the immune system learned to recognize new cancer targets it had previously ignored.

Vaccine-induced T cells developed into powerful subsets

Analysis of individual patients showed the vaccine-induced T cells matured into two critical subsets. One group developed a late-differentiated phenotype, acting as "ready-to-act" cytotoxic effector cells primed to attack cancer.

The other group developed a stem cell-like memory phenotype. These T cells can self-renew and provide a long-lasting reservoir of immune memory, which may explain the durability of the response observed over several years.

Most patients remained cancer-free for years

Eleven of the 14 patients remained relapse-free for up to six years following vaccination. This suggests the induced immune response provided durable protection against cancer recurrence in the majority of participants.

Recurrence occurred in three patients, offering crucial insights into potential mechanisms of immune escape. The patient with the weakest vaccine-induced T cell response relapsed but later achieved complete remission on anti-PD-1 therapy.

Recurrences revealed how cancers can evade immunity

The other two relapses highlighted specific vulnerabilities. One patient's tumor had low MHC class I expression, a critical system for presenting neoantigens to T cells. Under vaccine pressure, MHC class I-deficient cells grew out, effectively hiding from the immune attack.

The third patient was BRCA-positive and experienced a recurrence from a genetically distinct primary tumor, indicating the vaccine did not protect against a completely new cancer clone.

The study's findings demonstrate key aspects of this approach:

• Feasibility of creating individualized RNA vaccines for TNBC
• Persistence of functional, neoantigen-specific T cells for years
• Critical immune escape mechanisms that inform future drug combinations

Study paves way for next-generation cancer vaccines

This research, published in Nature, provides a strong proof-of-concept for neoantigen mRNA vaccines in an aggressive cancer type. The long-term persistence of vaccine-induced immunity is a particularly promising result for preventing metastatic relapse.

The identified escape mechanisms—weak T cell response, low MHC expression, and genetically distinct clones—directly guide next steps. Future approaches will likely combine such vaccines with agents that boost T cell potency or prevent MHC downregulation.

For patients with triple-negative breast cancer, which has few targeted therapies and a high risk of early metastatic relapse, this vaccine strategy represents a promising new avenue for post-surgical, adjuvant treatment to achieve long-term remission.