title: Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma.
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.
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, United States. mikayel.mkrtichyan@nih.gov
authors.forename: Mikayel
authors.initials: M
authors.lastname: Mkrtichyan
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.forename: Nina
authors.initials: N
authors.lastname: Movsesyan
authors.forename: Dmitry
authors.initials: D
authors.lastname: Loukinov
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Laust
authors.forename: Edward L
authors.initials: EL
authors.lastname: Nelson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D004268:DNA-Binding Proteins / Q000008:administration & dosage* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013737:Testis / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C499208:Ctcfl protein, mouse; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins