Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma

Mikayel Mkrtichyan, Anahit Ghochikyan, Hayk Davtyan, Nina Movsesyan, Dmitry Loukinov, Victor Lobanenkov, David H. Cribbs, Amanda K. Laust, Edward L. Nelson, Michael G. Agadjanyan

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Here, we analyze for the first time the immunological and therapeutic efficacy of a dendritic cell (DC) vaccine based on a cancer-testis antigen, Brother of regulator of imprinted sites (BORIS), an epigenetically acting tumor-promoting transcription factor. Vaccination of mice with DC loaded with truncated form of BORIS (DC/mBORIS) after 4T1 mammary tumor implantation induced strong anti-cancer immunity, inhibited tumor growth (18.75% of mice remained tumor-free), and dramatically lowered the number of spontaneous clonogenic metastases (50% of mice remained metastases-free). Higher numbers of immune effector CD4 and CD8 T cells infiltrated the tumors of vaccinated mice vs. control animals. Vaccination significantly decreased the number of myeloid-derived suppressor cells (MDSCs) infiltrating the tumor sites, but not MDSCs in the spleens of vaccinated animals. These data suggest that DC-based mBORIS vaccination strategies have significant anti-tumor activity in a therapeutic setting and will be more effective when combined with agents to attenuate tumor-associated immune suppression.

Original languageEnglish (US)
Pages (from-to)188-197
Number of pages10
JournalCellular Immunology
Volume270
Issue number2
DOIs
StatePublished - 2011

Keywords

  • 4T1 mammary carcinoma
  • Brother of regulator of imprinted sites (BORIS)
  • Dendritic cell (DC)-based vaccine
  • Immunotherapy of breast cancer
  • Myeloid derived suppressor cells (MDSC)
  • Tumor promoting transcription factor

ASJC Scopus subject areas

  • Immunology

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    Mkrtichyan, M., Ghochikyan, A., Davtyan, H., Movsesyan, N., Loukinov, D., Lobanenkov, V., Cribbs, D. H., Laust, A. K., Nelson, E. L., & Agadjanyan, M. G. (2011). Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma. Cellular Immunology, 270(2), 188-197. https://doi.org/10.1016/j.cellimm.2011.05.007