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

doi:10.1016/j.cellimm.2011.05.007

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

Pulmonary Disease

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23 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 language	English (US)
Pages (from-to)	188-197
Number of pages	10
Journal	Cellular Immunology
Volume	270
Issue number	2
DOIs	https://doi.org/10.1016/j.cellimm.2011.05.007
State	Published - 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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10.1016/j.cellimm.2011.05.007

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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

Mkrtichyan, M, Ghochikyan, A, Davtyan, H, Movsesyan, N, Loukinov, D, Lobanenkov, V, Cribbs, DH, Laust, AK, Nelson, EL & Agadjanyan, MG 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, vol. 270, no. 2, pp. 188-197. https://doi.org/10.1016/j.cellimm.2011.05.007

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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.",

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",

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

note = "Funding Information: We would like to thank students Mr. M. Shugay, Mr. J. Khlghatyan, Mr. Tiraturyan, Ms. A. Davtyan, and Ms. A. Hovakimyan for technical help and Dr. I. Petrushina for valuable comments. This work was supported by Susan Komen Foundation BCTR0707720 for ELN and NIH AG-20241 for DHC and MGA; NS-50895 for DHC and MGA; NS57395 for MGA grants and in part by Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH.",

year = "2011",

doi = "10.1016/j.cellimm.2011.05.007",

language = "English (US)",

volume = "270",

pages = "188--197",

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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.

N1 - Funding Information: We would like to thank students Mr. M. Shugay, Mr. J. Khlghatyan, Mr. Tiraturyan, Ms. A. Davtyan, and Ms. A. Hovakimyan for technical help and Dr. I. Petrushina for valuable comments. This work was supported by Susan Komen Foundation BCTR0707720 for ELN and NIH AG-20241 for DHC and MGA; NS-50895 for DHC and MGA; NS57395 for MGA grants and in part by Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH.

PY - 2011

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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.

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KW - Brother of regulator of imprinted sites (BORIS)

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KW - Immunotherapy of breast cancer

KW - Myeloid derived suppressor cells (MDSC)

KW - Tumor promoting transcription factor

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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