Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC

Area of Science:

• Oncology
• Immunology
• Vaccinology

Background:

• Triple-negative breast cancer (TNBC) has a high risk of early metastatic relapse.
• Effective therapeutic strategies for TNBC, especially post-surgery, are urgently needed.

Purpose of the Study:

• To evaluate the safety and efficacy of an individualized neoantigen mRNA vaccine in TNBC patients.
• To assess the durability and phenotype of vaccine-induced T cell responses.
• To explore potential immune escape mechanisms in TNBC.

Main Methods:

• Administered individualized neoantigen mRNA vaccine to 14 TNBC patients post-surgery.
• Monitored peripheral blood for T cell responses to neoantigens.
• Characterized T cell subsets and analyzed relapse patterns.
• Investigated tumor characteristics in patients who relapsed.

Main Results:

• High-magnitude, de novo T cell responses to multiple neoantigens were detected in most patients.
• Vaccine-induced T cells persisted for years, differentiating into effector and stem cell-like memory subsets.
• Eleven patients remained relapse-free for up to six years.
• Relapse was associated with weak T cell response, low MHC class I expression, or distinct primary tumor genetics.

Conclusions:

• Individualized RNA vaccines are feasible for TNBC treatment.
• Durable, functional neoantigen-specific T cell responses can be generated.
• Insights into immune escape mechanisms can guide future vaccine development and combination therapies.