DNA vaccination with CD44 variant isoform reduces mammary tumor local growth and lung metastasis

We have shown recently that cDNA vaccination, using a virtual lymph node, ameliorates experimental allergic encephalomyelitis. Successful cure from mammary tumor requires resolution of local tumor growth and metastases. We have examined whether targeting of CD44 cell surface adhesion molecule by cDN...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2008-06, Vol.7 (6), p.1615-1623
Main Authors: Wallach-Dayan, Shulamit Batya, Rubinstein, Ariel M, Hand, Carla, Breuer, Raphael, Naor, David
Format: Article
Language:English
Subjects:
Animals
Antibodies, Neoplasm - immunology
CD44 variant
Cell Proliferation
Clone Cells
DNA vaccination
Epitopes
Female
Humans
Hyaluronan Receptors - immunology
lung metastasis
Lung Neoplasms - immunology
Lung Neoplasms - secondary
Lymph Nodes - immunology
Mammary Neoplasms, Experimental - immunology
Mammary Neoplasms, Experimental - pathology
Mammary Neoplasms, Experimental - therapy
mammary tumor
Mice
Mice, Inbred BALB C
Phenotype
Protein Isoforms - immunology
Transfection
Tumor Cells, Cultured
Vaccination
Vaccines, DNA - therapeutic use
virtual lymph nodes
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Summary:We have shown recently that cDNA vaccination, using a virtual lymph node, ameliorates experimental allergic encephalomyelitis. Successful cure from mammary tumor requires resolution of local tumor growth and metastases. We have examined whether targeting of CD44 cell surface adhesion molecule by cDNA vaccination plays a role in resolving mammary tumor development. We show here that CD44 cDNA vaccination decreases the tumor mass and metastatic potential in experimental mammary tumor of BALB/c mice. Vaccination of mice, inoculated with the mammary tumors, by cDNA of CD44 variant (CD44v) but not by cDNA of standard CD44, markedly reduced local tumor development and lung metastasis. Concomitantly, transfection of CD44 antisense into a highly metastatic mammary tumor cell line disrupted the CD44 expression of the cells and reduced their ability to establish local tumors as well as metastatic colonies in the lung. Moreover, when CD44v, but not standard CD44 sense cDNA, was transfected into the poorly metastatic cell line, tumor development was markedly enhanced. It is possible therefore that DNA vaccination with a specific CD44v construct could induce an immune resistance to mammary tumor progression. [Mol Cancer Ther 2008;7(6):1615–23]
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-07-2383