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Cited by 37Immunotherapy and Immune ResponsesHER2/EGFR in Cancer ResearchBacteriophages and microbial interactions

Phage-Based Anti-HER2 Vaccination Can Circumvent Immune Tolerance against Breast Cancer

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Bartolacci, Caterina, Andreani, Cristina, Curcio, Claudia, Occhipinti, Sergio, Massaccesi, Luca, Giovarelli, Mirella, Galeazzi, Roberta, Iezzi, Manuela +5 more·2018·Cancer Immunology Research
DOI 10.1158/2326-6066.cir-18-0179

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Abstract

Δ16HER2 is a splice variant of HER2 and defined as the transforming isoform in HER2-positive breast cancer. It has been shown that Δ16HER2 promotes breast cancer aggressiveness and drug resistance. In the present work, we used in silico modeling to identify structural differences between Δ16HER2 and the wild-type HER2 proteins. We then developed DNA vaccines specifically against the Δ16HER2 isoform and showed that these immunotherapies hampered carcinogenesis in a breast cancer transplantable model. However, the vaccines failed to elicit immune protection in Δ16HER2 transgenic mice because of tolerogenic mechanisms toward the human HER2 self-antigen, a scenario commonly seen in HER2+ patients. Thus, we engineered bacteriophages with immunogenic epitopes of Δ16HER2 exposed on their coat for use as anticancer vaccines. These phage-based vaccines were able to break immune tolerance, triggering a protective anti-Δ16HER2 humoral response. These findings provide a rationale for the use of phage-based anti-HER2/Δ16HER2 vaccination as a safe and efficacious immunotherapy against HER2-positive breast cancers.

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  • M13 filamentous phages displaying HER2/neu epitopes elicited antigen-specific cytotoxic T lymphocyte responses and suppressed tumor growth in murine breast cancer models.

    “For example, M13 filamentous phages displaying HER2/neu epitopes elicited antigen-specific cytotoxic T lymphocyte responses and suppressed tumor growth in murine breast cancer models [80,81]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [80]

    The Introduction describes M13 phages displaying HER2 epitopes, and ‘Phages displaying antigen sequences can overcome immune tolerance’ reports smaller and fewer tumors in vaccinated D16HER2 mice. That section also reports increased tumor-infiltrating CD8+ T cells, but does not establish that they were antigen-specific cytotoxic T lymphocytes. The paper’s functional cytotoxic T-cell assays concern DNA vaccination, not phage vaccination. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Engineered phage vaccines displaying tumor-associated antigens or delivering immunostimulatory cargo have demonstrated robust antitumor immunity and survival benefits in multiple mouse models.

    “In parallel, engineered phage vaccines displaying tumor-associated antigens or delivering immunostimulatory cargo have demonstrated robust antitumor immunity and survival benefits in multiple mouse models [80–85]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [80]

    The Results section, “Phages displaying antigen sequences can overcome immune tolerance” (page unavailable), reports that antigen-displaying phages prolonged tumor latency and reduced tumor size and number in D16HER2 mice. The paper does not show a survival benefit or test its phage vaccines in multiple mouse models; its Discussion (page unavailable) describes the phages as self-adjuvating, not as delivering immunostimulatory cargo. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Together, these studies identify well-defined candidates for first-in-human evaluation.

    “Together, these studies identify well-defined candidates for first-in-human evaluation while underscoring the need to address translational barriers related to scalability, regulatory approval, and patient stratification.”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [80]

    The Discussion (page unavailable) identifies specific anti-HER2 phage vaccines and says the findings support their use in the clinical management of HER2-positive breast cancer. The evidence is from mice, however, and the paper does not identify the vaccines as ready or well-defined candidates for first-in-human evaluation. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Bartolacci, C., Andreani, C., Curcio, C., Occhipinti, S., Massaccesi, L., Giovarelli, M., Galeazzi, R., Iezzi, M., Tilio, M., Gambini, V., Wang, J., Marchini, C., & Amici, A.
Affiliations
  • Università di Camerino (IT)
  • University of Chieti-Pescara (IT)
  • University of Turin (IT)
  • Marche Polytechnic University (IT)
Corresponding author
  • Bartolacci, Caterina
  • Amici, Augusto
ORCID
Venue
Cancer Immunology Research
Publisher
American Association for Cancer Research (AACR)
Published
2018-12-01
Volume
6
Issue
12
Pages
1486-1498
ISSN
  • 2326-6066 (ISSN-L)
  • 2326-6074
DOI
10.1158/2326-6066.cir-18-0179
OpenAlex
W2897532536
Cited by
37
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 1 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 1
FWCI
1.61
Type
journal article
Language
en
Update notices
correction (2019-03-01)
Open access
Locations
  • Cancer Immunology Research (publishedVersion)
  • PubMed (publishedVersion)
  • Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion, cc-by-nc-nd)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
  • Unicam Scientific Publications (University of Camerino) (submittedVersion, other-oa)
Funders
  • Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG-11889, IG-9366)
  • Fondazione Umberto Veronesi (Umberto Veronesi Foundation) (Fellowship)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
Keywords
HER2-positive breast cancer, phage display, DNA vaccine, immune tolerance, self-tolerance, humoral immune response, transgenic mice, cancer immunotherapy
MeSH terms
Animals, Epitopes, Breast Neoplasms, Dendritic Cells, Exons, Female, Humans, Immune Tolerance, Mice, Inbred Strains, Mice, Transgenic, Immunotherapy, Adoptive, Bacteriophage M13, Erb-b2 Receptor Tyrosine Kinases, Vaccines, DNA, Cancer Vaccines

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