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Supplementary S3 from Phage-Based Anti-HER2 Vaccination Can Circumvent Immune Tolerance against Breast Cancer

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posted on 2023-04-03, 23:23 authored by Caterina Bartolacci, Cristina Andreani, Claudia Curcio, Sergio Occhipinti, Luca Massaccesi, Mirella Giovarelli, Roberta Galeazzi, Manuela Iezzi, Martina Tilio, Valentina Gambini, Junbiao Wang, Cristina Marchini, Augusto Amici

Further characterization of immune compartments upon DNA vaccination in Î"16HER2 mice

Funding

Italian Association of Cancer Research (AIRC)

University of Turin

Fondazione Umberto Veronesi

History

ARTICLE 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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    Cancer Immunology Research

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    Keywords

    Breast CancerCancer PreventionAnimal models of preventionComputational MethodsMolecular modelingImmunologyImmune responses to cancerTumor antigens/neoantigensTumor immunology animal modelsTumor resistance to immune responseImmunotherapyCancer vaccines

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