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Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant
Author(s) -
Loukinov Dmitri,
Ghochikyan Anahit,
Mkrtichyan Mikayel,
Ichim Thomas E.,
Lobanenkov Victor V.,
Cribbs David H.,
Agadjanyan Michael G.
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20953
Subject(s) - biology , cancer research , epigenetics , antigen , cancer , microbiology and biotechnology , immunology , gene , genetics
Abstract Cancer testis (CT) antigens are promising candidates for tumor vaccines due to their immunogenicity and tissue‐restricted expression. Recently, we identified a novel cancer testis gene, BORIS , whose expression is restricted to male testis after puberty and is strictly absent in non‐malignant female tissue. BORIS encodes a DNA‐binding protein that shares 11 zing finger (ZF) with transcription factor CTCF and differs at the N‐ and C‐termini. CTCF has been implicated in epigenetic regulation of imprinting, X chromosome inactivation, repression, and activation of cancer testis antigens. BORIS expression has been documented in cancers of diverse histological origin, including, but not limited to breast, prostate, ovary, gastric, liver, endometrial, glia, colon, and esophagus. Interestingly, BORIS induces demethylation and subsequent expression of many cancer‐testis genes, including MAGE‐A1 and NY‐ESO‐1, indicating that it is expressed very early in malignancy and might be an attractive candidate for immunotherapy. In this study we tested BORIS as a vaccine in a very aggressive, highly metastatic, and poorly immunogenic murine model of mammary carcinoma. Immunizations with a DNA encoding the mutant form of murine BORIS antigen (pmBORIS lacking DNA‐binding function) significantly prolonged survival, and inhibited tumor growth in BALB/c mice inoculated with 4T1 cells. Priming with pmBORIS mixed with molecular adjuvant and boosting with adenoviral vector expressing mBORIS was generally more effective, suggesting that the vaccination protocol could be further optimized. This is the first report demonstrating the feasibility of vaccination with a cancer associated epigenetic regulator for the induction of tumor inhibition. J. Cell. Biochem. 98: 1037–1043, 2006. © 2006 Wiley‐Liss, Inc.