Unraveling the use of vaccine therapy in HER2-positive breast cancer: a comprehensive review of current state and future perspectives
5 affiliations
- 1Oncology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II
- 2Clinical and Translational Oncology, Scuola Superiore Meridionale
- 3Medical Oncology, Breast & GYN Unit, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) “Dino Amadori”
- 4Department of Medicine (DMED), University of Udine
- 5U.O.C. Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino
Abstract
Background Despite significant advances in early detection and therapeutic strategies, breast cancer (BC) continues to pose a major public health challenge. The treatment of HER2-positive (HER2 +) BC has evolved substantially over recent years with the advent of monoclonal antibodies (mAbs), small-molecule tyrosine kinase inhibitors (TKIs), and antibody–drug conjugates (ADCs). Clinical progress has been significantly accelerated by a deeper understanding of the immune-regulatory properties of this subtype and its interactions with the tumor microenvironment. Despite the availability of effective HER2-targeted therapies, approximately one-third of patients develops resistance, highlighting the need for novel and more durable treatment strategies. Indeed, while current treatments have shown promising efficacy by promoting a “passive immune response,” they are associated with the emergence of resistant clones. Conversely, vaccine-based therapies are designed to elicit a durable “active immune response” by presenting tumor-associated antigens that stimulate the host immune system to recognize and eliminate malignant cells. This approach has the potential to generate long-lasting immunological memory, preventing recurrence, disease progression, and the emergence of immune-evasive tumor variants. Main body This review provides a comprehensive overview of cancer vaccines strategies for HER2 + BC with emphasis on their mechanisms, advantages, limitations, and their current developmental status. We explore diverse delivery platforms, including peptide/protein-based, nucleic acid, and cell-based vaccines. The clinical utility of these strategies is assessed across different disease settings: from prevention and interception in pre-invasive lesions, to the (neo)adjuvant treatment of early-stage BC and the management of advanced metastatic disease. While advanced-stage BC often presents an immunosuppressive tumor microenvironment that hinders vaccine efficacy, early-stage disease offers a more favorable immunological milieu for inducing robust and durable T-cell responses. Furthermore, we discuss emerging innovations such as neoantigen discovery, next-generation adjuvants (e.g., TLR and STING agonists), and novel combinatorial approaches with checkpoint inhibitors to overcome immune evasion. Conclusion Although most BC vaccines remain under clinical investigation, they represent a promising frontier for achieving disease control and the coming decade is expected to yield pivotal insights into their clinical utility and therapeutic potential.
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BibTeX
@article{caltavituro2026unraveling,
title = {{Unraveling the use of vaccine therapy in HER2-positive breast cancer: a comprehensive review of current state and future perspectives}},
author = {Aldo Caltavituro and Claudia Martinelli and Michela Palleschi and Miriam Pirolo and Vincenza Cantile and Roberto Buonaiuto and Carmine De Angelis and Fabio Puglisi and Lucia Del Mastro and Grazia Arpino and Mario Giuliano and Michelino De Laurentiis},
journal = {Journal of Experimental \& Clinical Cancer Research},
year = {2026},
month = jul,
doi = {10.1186/s13046-026-03789-1},
url = {https://doi.org/10.1186/s13046-026-03789-1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Unraveling the use of vaccine therapy in HER2-positive breast cancer: a comprehensive review of current state and future perspectives
AU - Aldo Caltavituro
AU - Claudia Martinelli
AU - Michela Palleschi
AU - Miriam Pirolo
AU - Vincenza Cantile
AU - Roberto Buonaiuto
AU - Carmine De Angelis
AU - Fabio Puglisi
AU - Lucia Del Mastro
AU - Grazia Arpino
AU - Mario Giuliano
AU - Michelino De Laurentiis
PY - 2026
DA - 2026/07/01
JO - Journal of Experimental & Clinical Cancer Research
DO - 10.1186/s13046-026-03789-1
UR - https://doi.org/10.1186/s13046-026-03789-1
AB - Background Despite significant advances in early detection and therapeutic strategies, breast cancer (BC) continues to pose a major public health challenge. The treatment of HER2-positive (HER2 +) BC has evolved substantially over recent years with the advent of monoclonal antibodies (mAbs), small-molecule tyrosine kinase inhibitors (TKIs), and antibody–drug conjugates (ADCs). Clinical progress has been significantly accelerated by a deeper understanding of the immune-regulatory properties of this subtype and its interactions with the tumor microenvironment. Despite the availability of effective HER2-targeted therapies, approximately one-third of patients develops resistance, highlighting the need for novel and more durable treatment strategies. Indeed, while current treatments have shown promising efficacy by promoting a “passive immune response,” they are associated with the emergence of resistant clones. Conversely, vaccine-based therapies are designed to elicit a durable “active immune response” by presenting tumor-associated antigens that stimulate the host immune system to recognize and eliminate malignant cells. This approach has the potential to generate long-lasting immunological memory, preventing recurrence, disease progression, and the emergence of immune-evasive tumor variants. Main body This review provides a comprehensive overview of cancer vaccines strategies for HER2 + BC with emphasis on their mechanisms, advantages, limitations, and their current developmental status. We explore diverse delivery platforms, including peptide/protein-based, nucleic acid, and cell-based vaccines. The clinical utility of these strategies is assessed across different disease settings: from prevention and interception in pre-invasive lesions, to the (neo)adjuvant treatment of early-stage BC and the management of advanced metastatic disease. While advanced-stage BC often presents an immunosuppressive tumor microenvironment that hinders vaccine efficacy, early-stage disease offers a more favorable immunological milieu for inducing robust and durable T-cell responses. Furthermore, we discuss emerging innovations such as neoantigen discovery, next-generation adjuvants (e.g., TLR and STING agonists), and novel combinatorial approaches with checkpoint inhibitors to overcome immune evasion. Conclusion Although most BC vaccines remain under clinical investigation, they represent a promising frontier for achieving disease control and the coming decade is expected to yield pivotal insights into their clinical utility and therapeutic potential.
SN - 1756-9966
ER -