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Cancer Immunology, Immunotherapy

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01.11.2008 | Symposium Paper

The “A, B and C” of Her-2 DNA vaccine development

verfasst von: Wei-Zen Wei, Jennifer Jacob, Olga Radkevich-Brown, Paula Whittington, Yi-chi M. Kong

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2008

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Abstract

Introduction

The development of Her-2 DNA vaccine has progressed through three phases that can be categorized as phase “A”: the pursuit of Her-2 as a tumor-associated “antigen”, phase “B”: tilting the “balance” between tumor immunity and autoimmunity and phase “C”: the on-going “clinical trials”.

Materials and methods

In phase “A”, a panel of human ErbB-2 or Her-2 plasmids were constructed to encode non-transforming Her-2 derivatives. The immunogenicity and anti-tumor activity of Her-2 DNA vaccines were tested in human Her-2 transgenic mice with or without the depletion of regulatory T cells (Tregs). However, Treg depletion or other immune modulating regimens may increase the risk of autoimmunity. In phase “B”, the balance between tumor immunity and autoimmunity was assessed by monitoring the development of experimental autoimmune thyroiditis (EAT). To test the efficacy of Her-2 DNA vaccines in cancer patients, clinical trials have been initiated in phase “C”.

Results and conclusions

Significant anti-Her-2 and anti-tumor activity was observed when Her-2 transgenic mice were electro-vaccinated after Treg depletion. Susceptibility to EAT was also enhanced by Treg depletion and there was mutual amplification between Her-2 immunity and EAT development. Although Tregs regulate both EAT and Her-2 immunity, their effector mechanisms may differ. It may be possible to amplify tumor immunity with improved strategies that can by-pass undue autoimmunity. Critical information will be revealed in the next decade to expedite the development of cancer vaccines.

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Titel: The “A, B and C” of Her-2 DNA vaccine development
verfasst von: Wei-Zen Wei
Jennifer Jacob
Olga Radkevich-Brown
Paula Whittington
Yi-chi M. Kong
Publikationsdatum: 01.11.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0464-y

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Results and conclusions

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