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Research Articles: Therapeutics, Targets, and Development

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

¹ The Lautenberg Center for General and Tumor Immunology and ² The Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, The Hebrew University-Hadassah Medical School, Jerusalem, Israel; ³ The Kenneth S. Warren Institute, Ossining, New York; and ⁴ Pulmonary Center and Department of Pathology, Boston University School of Medicine, Boston, Massachusetts

Requests for reprints: Shulamit Batya Wallach-Dayan, The Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, The Hebrew University-Hadassah Medical School, P.O. Box 12000, Jerusalem, Israel. Phone: 972-2-6776622; Fax: 972-2-6435897. E-mail: Wallach-Dayan{at}hadassah.org.il

Abstract

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]

Grant support: German-Israeli Foundation for Scientific Research and Development and Deutsche Krebshilfe, Mildred Scheel Stiftung.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 12/10/07; revised 3/20/08; accepted 3/28/08.