Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant

Dmitri Loukinov, Anahit Ghochikyan, Mikayel Mkrtichyan, Thomas E. Ichim, Victor V. Lobanenkov, David H. Cribbs, Michael C. Agadjanyan

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1037-1043
Number of pages7
JournalJournal of cellular biochemistry
Volume98
Issue number5
DOIs
StatePublished - Aug 1 2006

Fingerprint

Testicular Neoplasms
Tumors
Vaccination
Transcription Factors
Antigens
DNA
Genes
Tissue
Neoplasm Genes
Immunization
Neoplasms
Cancer Vaccines
Epigenomics
DNA-Binding Proteins
Chromosomes
Liver
Vaccines
X Chromosome Inactivation
Chemical activation
Puberty

Keywords

  • BORIS
  • Breast cancer
  • CT antigens
  • Mammary tumor
  • Vaccine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Loukinov, D., Ghochikyan, A., Mkrtichyan, M., Ichim, T. E., Lobanenkov, V. V., Cribbs, D. H., & Agadjanyan, M. C. (2006). Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. Journal of cellular biochemistry, 98(5), 1037-1043. https://doi.org/10.1002/jcb.20953

Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. / Loukinov, Dmitri; Ghochikyan, Anahit; Mkrtichyan, Mikayel; Ichim, Thomas E.; Lobanenkov, Victor V.; Cribbs, David H.; Agadjanyan, Michael C.

In: Journal of cellular biochemistry, Vol. 98, No. 5, 01.08.2006, p. 1037-1043.

Research output: Contribution to journalArticle

Loukinov, D, Ghochikyan, A, Mkrtichyan, M, Ichim, TE, Lobanenkov, VV, Cribbs, DH & Agadjanyan, MC 2006, 'Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant', Journal of cellular biochemistry, vol. 98, no. 5, pp. 1037-1043. https://doi.org/10.1002/jcb.20953
Loukinov, Dmitri ; Ghochikyan, Anahit ; Mkrtichyan, Mikayel ; Ichim, Thomas E. ; Lobanenkov, Victor V. ; Cribbs, David H. ; Agadjanyan, Michael C. / Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. In: Journal of cellular biochemistry. 2006 ; Vol. 98, No. 5. pp. 1037-1043.
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