This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ortmann, D. Articles by Reincke, M. Search for Related Content PubMed PubMed Citation Articles by Ortmann, D. Articles by Reincke, M.

Steroidogenic Acute Regulatory (StAR)-Directed Immunotherapy Protects against Tumor Growth of StAR-Expressing Sp2-0 Cells in a Rodent Adrenocortical Carcinoma Model

Department of Internal Medicine 2, Division of Endocrinology (D.O., F.B., K.S., M.S., M.R.) and Division of Gastroenterology (M.G.), University Hospital of Freiburg, D-79106 Freiburg, Germany; and Institute of Medical Microbiology and Hygiene, Department of Virology (J.H.), University of Freiburg, D-79104 Freiburg, Germany

Address all correspondence and requests for reprints to: Martin Reincke, M.D., Division of Endocrinology, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany. E-mail: reincke{at}med1 ukl.uni-freiburg.de.

Adrenocortical carcinoma (ACC) is a highly malignant tumor with poor response to classical antitumor therapy. Steroidogenic acute regulatory (StAR) protein is expressed in most human ACCs. The aim of this study was to induce antitumoral T cells directed against StAR in a murine tumor model. Because a suitable syngenic adrenocortical mouse tumor model is lacking, we established a clone of the mouse myeloma Sp2-0 tumor cell line stably expressing murine StAR (Sp2-mStAR). Using repeated im injections of plasmid DNA encoding mStAR followed by infection with a recombinant vaccinia virus (rVV) expressing mStAR, we induced a cytotoxic T-cell response as measured by enzyme-linked immunospot assay. To demonstrate antitumor activity of the vaccination procedure, mice were treated as follows: group A, mice immunized with plasmids and rVV encoding mStAR receiving Sp2-mStAR cells; control group B, mice immunized with the empty plasmid and the empty rVV receiving Sp2-mStAR cells; control group C, mice immunized with the empty plasmid and rVV encoding P450 side-chain cleavage enzyme receiving Sp2-mStAR cells; and control group D, mice immunized with plasmid and rVV encoding mStAR receiving parental Sp2-0 cells. A high proportion (89–100%) of the control groups B, C, and D developed subcutaneous tumors. In contrast, immunization specific for mStAR (group A) was highly protective against tumor growth (percentage of tumor-free animals, 67%; P < 0.001 vs. controls). In summary, these results show that T-cell tolerance toward mStAR can be broken, resulting in antitumoral immunity. Thus, StAR represents a candidate target antigen for immunotherapeutic strategies against ACC.

This article has been cited by other articles:

				L. S. Kirschner Emerging Treatment Strategies for Adrenocortical Carcinoma: A New Hope J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 14 - 21. [Abstract] [Full Text] [PDF]

				U. Fassnacht, A. Ackermann, P. Staeheli, and J. Hausmann Immunization with dendritic cells can break immunological ignorance toward a persisting virus in the central nervous system and induce partial protection against intracerebral viral challenge J. Gen. Virol., August 1, 2004; 85(8): 2379 - 2387. [Abstract] [Full Text] [PDF]