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

Cancer Immunology Research - Tập 6 Số 12 - Trang 1486-1498 - 2018
Caterina Bartolacci1, Cristina Andreani1, Claudia Curcio2,3, Sergio Occhipinti3, Luca Massaccesi4, Mirella Giovarelli3, Roberta Galeazzi4, Manuela Iezzi2, Martina Tilio1, Valentina Gambini1, Junbiao Wang1, Cristina Marchini1, Augusto Amici1
11Department of Biosciences and Veterinary Medicine University of Camerino, Camerino, Italy.
22Aging Research Centre, G. d'Annunzio University, Chieti, Italy.
33Department of Molecular Biotechnology and Health Sciences, Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy.
44Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.

Tóm tắt

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.

Từ khóa


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