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Breast Cancer Research
Published in: Breast Cancer Research 1/2011

Open Access 01-02-2011 | Research article

Vaccination with human anti-trastuzumab anti-idiotype scFv reverses HER2 immunological tolerance and induces tumor immunity in MMTV.f.huHER2(Fo5) mice

Authors: Maha Z Ladjemi, Thierry Chardes, Stephanie Corgnac, Veronique Garambois, Sebastien Morisseau, Bruno Robert, Caroline Bascoul-Mollevi, Imade Ait Arsa, William Jacot, Jean-Pierre Pouget, Andre Pelegrin, Isabelle Navarro-Teulon

Published in: Breast Cancer Research | Issue 1/2011

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Abstract

Introduction

Novel adjuvant therapies are needed to prevent metastatic relapses in HER2-expressing breast cancer. Here, we tested whether trastuzumab-selected single-chain Fv (scFv) could be used to develop an anti-idiotype-based vaccine to inhibit growth of HER2-positive tumor cells in vitro and in vivo through induction of long-lasting HER-specific immunity.

Methods

BALB/c mice were immunized with anti-trastuzumab anti-idiotype (anti-Id) scFv (scFv40 and scFv69), which mimic human HER2. Their sera were assessed for the presence of HER2-specific Ab1' antibodies and for their ability to reduce viability of SK-OV-3 cells, a HER2-positive cancer cell line, in nude mice. MMTV.f.huHER2(Fo5) transgenic mice were immunized with scFv40 and scFv69 and, then, growth inhibition of spontaneous HER2-positive mammary tumors, humoral response, antibody isotype as well as splenocyte secretion of IL2 and IFN-γ were evaluated.

Results

Adoptively-transferred sera from BALB/c mice immunized with scFv40 and scFv69 contain anti-HER2 Ab1' antibodies that can efficiently inhibit growth of SK-OV-3 cell tumors in nude mice. Similarly, prophylactic vaccination with anti-Id scFv69 fully protects virgin or primiparous FVB-MMTV.f.huHER2(Fo5) females from developing spontaneous mammary tumors. Moreover, such vaccination elicits an anti-HER2 Ab1' immune response together with a scFv69-specific Th1 response with IL2 and IFN-γ cytokine secretion.

Conclusions

Anti-trastuzumab anti-Id scFv69, used as a therapeutic or prophylactic vaccine, protects mice from developing HER2-positive mammary tumors by inducing both anti-HER2 Ab1' antibody production and an anti-HER2 Th2-dependent immune response. These results suggest that scFv69 could be used as an anti-Id-based vaccine for adjuvant therapy of patients with HER2-positive tumors to reverse immunological tolerance to HER2.
Appendix
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Metadata
Title
Vaccination with human anti-trastuzumab anti-idiotype scFv reverses HER2 immunological tolerance and induces tumor immunity in MMTV.f.huHER2(Fo5) mice
Authors
Maha Z Ladjemi
Thierry Chardes
Stephanie Corgnac
Veronique Garambois
Sebastien Morisseau
Bruno Robert
Caroline Bascoul-Mollevi
Imade Ait Arsa
William Jacot
Jean-Pierre Pouget
Andre Pelegrin
Isabelle Navarro-Teulon
Publication date
01-02-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2826

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