Author/Authors :
Mkrtichyan، نويسنده , , Mikayel and Ghochikyan، نويسنده , , Anahit Pews-Davtyan، نويسنده , , Hayk and Movsesyan، نويسنده , , Nina and Loukinov، نويسنده , , Dmitry and Lobanenkov، نويسنده , , Victor and Cribbs، نويسنده , , David H. and Laust، نويسنده , , Amanda K. and Nelson، نويسنده , , Edward L. and Agadjanyan، نويسنده , , Michael G.، نويسنده ,
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.
Keywords :
Immunotherapy of breast cancer , Myeloid derived suppressor cells (MDSC)Cancer-testis antigen (CTA) , Dendritic cell (DC)-based vaccine , Brother of regulator of imprinted sites (BORIS) , Tumor promoting transcription factor , 4T1 mammary carcinoma