A multitargeting nanoparticle-based vaccine for enhanced anticancer immunotherapy in HER2-Positive breast cancer.

Authors

Sen Liu, Yiqiang Zhu, Tao Chen, Xiaoqing Liu, Jintao Lai, Meilin Hu, Yaoming Liu, Haiyue Rao, Bin Zhang, Shiqi Xiao, Haojie Peng, Taizhen Liang, Lixiang Xie, Guochang Qiu, Shan Li, Xiancai Ma

Published in

Materials today. Bio. Volume 40. Pages 103524. Epub Aug 03, 2026.

Abstract

Tumor vaccines represent promising strategies for cancer immunotherapy. However, their application remains restricted in HER2-positive breast cancer due to poor immunogenicity and inefficient antigen presentation. Herein, a multitargeting HER2 nanoparticle vaccine, HER2_aHPF, is developed by co-displaying the HER2 extracellular domain and AE37 T-cell epitope on a Helicobacter pylori ferritin nanoparticle via SpyTag/SpyCatcher conjugation. The nanoparticle vaccine exhibits structural homogeneity, enhanced lymphatic drainage, and high stability during freeze-thaw cycles and long-term storage, with retained immunogenicity after repeated freeze-thaw treatment. WH peptide-mediated DC targeting, in combination with the ferritin scaffold, enhances antigen uptake and DC maturation. In BALB/c mice, CpG and fullerenol dual-adjuvanted HER2_aHPF elicits robust HER2-specific humoral and cellular immunity, characterized by high-titer antibodies, polyfunctional CD4⁺ and CD8⁺ T cells, and expanded effector-memory T cells. Prophylactic and therapeutic vaccination markedly inhibits primary tumor growth and lung metastasis in mouse and human HER2-positive 4T1 models. Mechanistically, HER2_aHPF reduces myeloid-derived suppressor cells and regulatory T cells, increases cytotoxic T-cell infiltration, and maintains a favorable in vivo safety profile. Combination with anti-PD-1 and anti-CD47 antibodies further enhances T-cell activity and tumor control, demonstrating strong synergy between active vaccination and dual immune checkpoint blockade. These findings establish HER2_aHPF as a versatile nanoparticle vaccine platform with clinical translation potential for HER2-positive cancer immunotherapy.

PMID:
42602399
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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