Active immunization with a Her-2/neu-targeting Multi-peptide B cell vaccine prevents lung metastases formation from Her-2/neu breast cancer in a mouse model

Autor: Joshua Tobias, Mirjana Drinić, Sandra Högler, Katharina Ambroz, Karin Baier, Petra Kodajova, Erwin Tomasich, Anna S. Berghoff, Anna Schmid, Erika Garner-Spitzer, Lukas Kenner, Michael Kundi, Christoph C. Zielinski, Ursula Wiedermann
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Translational Oncology, Vol 19, Iss , Pp 101378- (2022)
Druh dokumentu: article
ISSN: 1936-5233
DOI: 10.1016/j.tranon.2022.101378
Popis: In pre-clinical and clinical settings, active immunization with a Her-2/neu vaccine (HerVaxx), comprising B-cell peptide from Trastuzumab binding site, has been shown to reduce primary tumor growth via induction of polyclonal anti-tumor immune responses and immunological memory. Here, we tested the combination of HerVaxx and the recently identified B-cell epitope/mimotope of Pertuzumab, i.e. a multi-peptide B-cell vaccine, for preventing Her-2/neu lung metastases formation in a mouse model. Active immunization with the multi-peptide vaccine was associated with decreased lung weights, and histological evaluation of the lungs showed that the significant reduction of lung metastases was associated with increased CD4+ and CD8+ T cell infiltration. Notably, along with the overall reduction of lungs weights and Her-2 positive metastases, a formation of Her-2/neu-negative tumors but with increased PD-L1 expression was observed. Our results might pave the way to a multi-peptide B-cell Her-2/neu vaccine serving as a secondary intervention in adjuvant settings to prevent tumor recurrence and spread. Moreover, combination therapy targeting PD-L1 may result in total remission of metastases. Such a therapy may be used clinically to alternately target Her-2/neu and PD-L1 in metastatic breast cancer.
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