Erbb2 DNA Vaccine Combined with Regulatory T Cell Deletion Enhances Antibody Response and Reveals Latent Low-Avidity T Cells: Potential and Limits of Its Therapeutic Efficacy
Open Access
- 1 June 2010
- journal article
- Published by The American Association of Immunologists
- Vol. 184 (11), 6124-6132
- https://doi.org/10.4049/jimmunol.0901215
Abstract
Rat (r)Erbb2 transgenic BALB-neuT mice genetically predestined to develop multiple invasive carcinomas allow an assessment of the potential of a vaccine against the stages of cancer progression. Because of rErbb2 expression in the thymus and its overexpression in the mammary gland, CD8+ T cell clones reacting at high avidity with dominant rErbb2 epitopes are deleted in these mice. In BALB-neuT mice with diffuse and invasive in situ lesions and almost palpable carcinomas, a temporary regulatory T cells depletion combined with anti-rErbb2 vaccine markedly enhanced the anti-rErbb2 Ab response and allowed the expansion of latent pools of low-avidity CD8+ T cells bearing TCRs repertoire reacting with the rErbb2 dominant peptide. This combination of a higher Ab response and activation of a low-avidity cytotoxic response persistently blocked tumor progression at stages in which the vaccine alone was ineffective. However, when diffuse and invasive microscopic cancers become almost palpable, this combination was no longer able to secure a significant extension of mice survival.Keywords
This publication has 45 references indexed in Scilit:
- Antibody association with HER-2/neu–targeted vaccine enhances CD8+ T cell responses in mice through Fc-mediated activation of DCsJCI Insight, 2008
- Protective Immunity Againstneu-Positive Carcinomas Elicited by Electroporation of Plasmids Encoding Decreasing Fragments of Rat Neu Extracellular DomainHuman Gene Therapy, 2008
- Systemic Spread Is an Early Step in Breast CancerCancer Cell, 2008
- DNA immunization using constant-current electroporation affords long-term protection from autochthonous mammary carcinomas in cancer-prone transgenic miceCancer Gene Therapy, 2007
- Mobilizing the low-avidity T cell repertoire to kill tumorsSeminars in Cancer Biology, 2007
- Immunosurveillance ofErbb2Carcinogenesis in Transgenic Mice Is Concealed by a Dominant Regulatory T-Cell Self-ToleranceCancer Research, 2006
- Regulatory T cells, tumour immunity and immunotherapyNature Reviews Immunology, 2006
- Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: Potential targets of anti-cancer therapyEuropean Journal Of Cancer, 2006
- Vaccines for tumour preventionNature Reviews Cancer, 2006
- Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivityBlood, 2003