Cytotoxicity of Cord Blood Derived Her2/neu-specific Cytotoxic T Lymphocytes against Human Breast Cancer in vitro and in vivo View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-01

AUTHORS

Peng Wang, Corey M. Munger, Avadhut D. Joshi, Samuel J. Pirruccello, Shantaram S. Joshi

ABSTRACT

The Her2/neu oncogene encodes a transmembrane protein with homology to the epidermal growth factor receptor. Overexpression of this gene contributes to the aggressiveness of breast cancer and poor prognosis. Therefore, Her2/neu is an ideal target molecule for generating effective cytotoxic T lymphocytes (CTLs) against breast cancers. This study reports on the generation of Her2/neu-specific CTL from umbilical cord blood mononuclear cells (UCBC) using dendritic cells primed with Her2/neu-derived peptide (KIFGSLAFL, E75) for immunostimulation. The CTLs showed specific cytotoxicity to Her2/neu high expressing MDA-453 but not toward Her2/neu low expressing MDA-231 human breast cancer cells. Similarly generated CTLs stimulated with irrelevant peptide pulsed dendritic cells did not show significant cytotoxicity towards breast cancer targets. The phenotypes of cells in culture showed high percentage of CD3+, CD4+ and CD8+T cells as determined by flow cytometry. However, the antibody mediated blocking assay demonstrated that only HLA-Class I restricted CD8+ cells are involved in the cytotoxicity. Furthermore, in vivo studies showed that treatment of SCID mice bearing MDA-453 tumor with Her2/neu-specific CTLs resulted in significant inhibition of tumor growth compared to untreated tumor bearing control mice. These results demonstrate that human umbilical cord blood mononuclear cells are a good source for generating Her2/neu-specific CTLs against human breast cancer both in vitro and in vivo. More... »

PAGES

15-23

References to SciGraph publications

  • 2001-10. The Role of c-erbB-2/HER2/neu in Breast Cancer Progression and Metastasis in JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1023/b:brea.0000010688.55353.a8

    DOI

    http://dx.doi.org/10.1023/b:brea.0000010688.55353.a8

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/14997051


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