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 language | English (US) |
|---|---|
| Pages (from-to) | 188-197 |
| Number of pages | 10 |
| Journal | Cellular Immunology |
| Volume | 270 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 6 2011 |
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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
Cite this
Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma. / Mkrtichyan, Mikayel; Ghochikyan, Anahit; Davtyan, Hayk; Movsesyan, Nina; Loukinov, Dmitry; Lobanenkov, Victor; Cribbs, David H.; Laust, Amanda K.; Nelson, Edward L.; Agadjanyan, Michael G.
In: Cellular Immunology, Vol. 270, No. 2, 06.06.2011, p. 188-197.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma
AU - Mkrtichyan, Mikayel
AU - Ghochikyan, Anahit
AU - Davtyan, Hayk
AU - Movsesyan, Nina
AU - Loukinov, Dmitry
AU - Lobanenkov, Victor
AU - Cribbs, David H.
AU - Laust, Amanda K.
AU - Nelson, Edward L.
AU - Agadjanyan, Michael G.
PY - 2011/6/6
Y1 - 2011/6/6
N2 - 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.
AB - 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.
KW - 4T1 mammary carcinoma
KW - Brother of regulator of imprinted sites (BORIS)
KW - Dendritic cell (DC)-based vaccine
KW - Immunotherapy of breast cancer
KW - Myeloid derived suppressor cells (MDSC)
KW - Tumor promoting transcription factor
UR - http://www.scopus.com/inward/record.url?scp=80051667961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051667961&partnerID=8YFLogxK
U2 - 10.1016/j.cellimm.2011.05.007
DO - 10.1016/j.cellimm.2011.05.007
M3 - Article
C2 - 21641588
AN - SCOPUS:80051667961
VL - 270
SP - 188
EP - 197
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 2
ER -