AUTHOR=Lee Sang Beom , Qian Jianfei , Pan Jing , Sei Shizuko , Wang Yian , You Ming 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1638526

DOI=10.3389/fimmu.2025.1638526

ISSN=1664-3224

ABSTRACT=Triple-negative breast cancer (TNBC) is associated with a poor prognosis due to high recurrence rates and a lack of targeted therapies. Significant challenges in developing efficacious TNBC cancer vaccines are tumor antigen heterogeneity and the risk of antigen-negative variant escape, where target antigen-negative tumor cells can emerge, evading single-antigen vaccine-induced immunity, and drive tumor growth. To address this, we developed TNBCvax, a multi-antigen, multi-peptide vaccine targeting three tumor-associated antigens overexpressed in TNBC: TOP2A, HIF-1α and IGF-1R. The immune preventive effect of TNBCvax was evaluated in both a syngeneic M6 TNBC tumor graft model and the C3(1)/Tag genetically engineered mouse model of TNBC. Our findings demonstrate that TNBCvax significantly reduced tumor development and progression, compared to single-antigen vaccines. TNBCvax induced a robust tumor-associated antigen-specific immune response as evidenced by the increased infiltration of CD3+ T cells, particularly CD8+ T cells, with elevated levels of granzyme B and tumor necrosis factor alpha (TNF-α). TNBCvax was well-tolerated with no significant major organ toxicities, supporting its potential safety in the clinic. In conclusion, TNBCvax offers a promising immunopreventive strategy against TNBC by targeting multiple antigens to provide a broader and more robust immune coverage against TNBC antigens while reducing the risk of antigen-negative variant escape.