Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion.

Details

Serval ID
serval:BIB_AABEA932059C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion.
Journal
Cancer Research
Author(s)
Czerniecki B.J., Koski G.K., Koldovsky U., Xu S., Cohen P.A., Mick R., Nisenbaum H., Pasha T., Xu M., Fox K.R., Weinstein S., Orel S.G., Vonderheide R., Coukos G., DeMichele A., Araujo L., Spitz F.R., Rosen M., Levine B.L., June C., Zhang P.J.
ISSN
0008-5472 (Print)
ISSN-L
0008-5472
Publication state
Published
Issued date
2007
Volume
67
Number
4
Pages
1842-1852
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Overexpression of HER-2/neu (c-erbB2) is associated with increased risk of recurrent disease in ductal carcinoma in situ (DCIS) and a poorer prognosis in node-positive breast cancer. We therefore examined the early immunotherapeutic targeting of HER-2/neu in DCIS. Before surgical resection, HER-2/neu(pos) DCIS patients (n = 13) received 4 weekly vaccinations of dendritic cells pulsed with HER-2/neu HLA class I and II peptides. The vaccine dendritic cells were activated in vitro with IFN-gamma and bacterial lipopolysaccharide to become highly polarized DC1-type dendritic cells that secrete high levels of interleukin-12p70 (IL-12p70). Intranodal delivery of dendritic cells supplied both antigenic stimulation and a synchronized preconditioned burst of IL-12p70 production directly to the anatomic site of T-cell sensitization. Before vaccination, many subjects possessed HER-2/neu-HLA-A2 tetramer-staining CD8(pos) T cells that expressed low levels of CD28 and high levels of the inhibitory B7 ligand CTLA-4, but this ratio inverted after vaccination. The vaccinated subjects also showed high rates of peptide-specific sensitization for both IFN-gamma-secreting CD4(pos) (85%) and CD8(pos) (80%) T cells, with recognition of antigenically relevant breast cancer lines, accumulation of T and B lymphocytes in the breast, and induction of complement-dependent, tumor-lytic antibodies. Seven of 11 evaluable patients also showed markedly decreased HER-2/neu expression in surgical tumor specimens, often with measurable decreases in residual DCIS, suggesting an active process of "immunoediting" for HER-2/neu-expressing tumor cells following vaccination. DC1 vaccination strategies may therefore have potential for both the prevention and the treatment of early breast cancer.
Keywords
Antibody-Dependent Cell Cytotoxicity, Breast Neoplasms/immunology, Breast Neoplasms/therapy, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, Carcinoma, Intraductal, Noninfiltrating/immunology, Carcinoma, Intraductal, Noninfiltrating/therapy, Dendritic Cells/immunology, Dendritic Cells/secretion, Humans, Immunotherapy, Adoptive/methods, Interferon-gamma/immunology, Interferon-gamma/pharmacology, Interleukin-12/immunology, Interleukin-12/secretion, Leukapheresis, Lipopolysaccharides/immunology, Lipopolysaccharides/pharmacology, Monocytes/drug effects, Monocytes/immunology, Receptor, erbB-2/immunology, T-Lymphocytes/immunology
Pubmed
Web of science
Open Access
Yes
Create date
14/10/2014 11:43
Last modification date
20/08/2019 15:14
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