Immunoprevention of triple-negative breast cancer with a novel multivalent vaccine

Area of Science:

• Oncology
• Immunology
• Vaccine Development

Background:

• Triple-negative breast cancer (TNBC) presents a poor prognosis due to high recurrence and limited targeted therapies.
• Tumor antigen heterogeneity and antigen-negative variant escape pose significant challenges for TNBC vaccine efficacy.

Purpose of the Study:

• To develop and evaluate TNBCvax, a multi-antigen vaccine targeting TOP2A, HIF-1α, and IGF-1R, to overcome TNBC challenges.
• To assess the immunopreventive efficacy and safety of TNBCvax in preclinical TNBC models.

Main Methods:

• Development of TNBCvax, a multi-peptide vaccine targeting three TNBC-overexpressed antigens.
• Evaluation of TNBCvax in a syngeneic M6 TNBC tumor graft model and the C3(1)/Tag genetically engineered mouse model.
• Assessment of tumor development, progression, immune response (T cell infiltration, granzyme B, TNF-α), and toxicity.

Main Results:

• TNBCvax significantly reduced tumor development and progression compared to single-antigen vaccines.
• TNBCvax induced a robust antigen-specific immune response, including increased CD8+ T cell infiltration and elevated granzyme B and TNF-α levels.
• The vaccine demonstrated a favorable safety profile with no significant major organ toxicities.

Conclusions:

• TNBCvax presents a promising immunopreventive strategy for TNBC by employing a multi-antigen approach.
• Targeting multiple antigens broadens immune coverage and mitigates the risk of antigen-negative variant escape in TNBC.
• The vaccine's efficacy and safety profile support its potential for clinical translation in TNBC prevention.