ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1638526
This article is part of the Research TopicAdvances in Therapeutic Cancer Vaccines-Mechanisms and developmentView all articles
Immunoprevention of Triple-Negative Breast Cancer with A Novel Multivalent Vaccine
Provisionally accepted
- 1Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute, Weill Cornell College of Medicine, Houston, United States
- 2Center for Translational Research in Hematological Malignancies, Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Weill Cornell College of Medicine, Houston, United States
- 3Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, United States
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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-IR. 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.
Keywords: Triple-negative breast cancer (TNBC), Topoisomerase 2 alpha (TOP2A), Hypoxia inducible factor-1α (HIF-1α), Insulin-like growth factor-I receptor (IGF-IR) Peptide vaccine, Immunoprevention, Multi-antigen multi-peptide (TNBCvax) vaccine
Received: 30 May 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Lee, Qian, Pan, Sei, Wang and You. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ming You, Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute, Weill Cornell College of Medicine, Houston, United States
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