4.5 Article

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

Journal

CELLULAR IMMUNOLOGY
Volume 270, Issue 2, Pages 188-197

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2011.05.007

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

Funding

  1. Susan Komen Foundation [BCTR0707720]
  2. NIH [AG-20241]
  3. National Institute of Allergy and Infectious Diseases, NIH [NS-50895, NS57395]
  4. NATIONAL CANCER INSTITUTE [T32CA009054] Funding Source: NIH RePORTER
  5. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI001021] Funding Source: NIH RePORTER
  6. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS057395, R01NS050895] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE ON AGING [R01AG020241] Funding Source: NIH RePORTER

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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. (C) 2011 Elsevier Inc. All rights reserved.

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