Preparation of Triple-Negative Breast Cancer Vaccine through Electrofusion with Day-3 Dendritic Cells

• Published in: PloS one Vol. 9; no. 7; p. e102197
• Main Authors: Zhang, Peng, Yi, Shuhong, Li, Xi, Liu, Ruilei, Jiang, Hua, Huang, Zenan, Liu, Yu, Wu, Juekun, Huang, Yong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.07.2014; Public Library of Science (PLoS)
• Subjects: Anticancer properties; Antigen-presenting cells; Antigens; Antitumor activity; Apoptosis; B cells; Biological effects; Biology and Life Sciences; Breast cancer; Cancer; Cancer therapies; Cancer Vaccines; Cell culture; Cell Fusion - methods; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Cytotoxicity; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Electricity; Electrofusion; Fluorescence; Humans; Immune system; Immunization; Immunology; Immunotherapy; Immunotherapy, Adoptive; Interferon-gamma - secretion; Interleukin 12; Interleukin 6; Interleukin-12 - secretion; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Monocytes; Morphology; Peripheral blood; Phenotype; Phenotypes; Research and Analysis Methods; Surface markers; Surgery; T cell receptors; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - secretion; Thyroid gland; Time Factors; Triple Negative Breast Neoplasms - immunology; Triple Negative Breast Neoplasms - pathology; Triple Negative Breast Neoplasms - prevention & control; Tumor necrosis factor; Tumor necrosis factor-α; Tumors; Vaccines; γ-Interferon; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0102197

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) in human immune system. DC-based tumor vaccine has met with some success in specific malignancies, inclusive of breast cancer. In this study, we electrofused MDA-MB-231 breast cancer cell line with day-3 DCs derived from peripheral blood monocytes, and explored the biological characteristics of fusion vaccine and its anti-tumor effects in vitro. Day-3 mature DCs were generated from day-2 immature DCs by adding cocktails composed of TNF-α, IL-1β, IL-6 and PEG2. Day-3 mature DCs were identified and electofused with breast cancer cells to generate fusion vaccine. Phenotype of fusion cells were identified by fluorescence microscope and flow cytometer. The fusion vaccine was evaluated for T cell proliferation, secretion of IL-12 and IFN-γ, and induction of tumor-specific CTL response. Despite differences in morphology, day-3 and day-7 DC expressed similar surface markers. The secretion of IL-12 and IFN-γ in fusion vaccine group was much higher than that in the control group. Compared with control group, DC-tumor fusion vaccine could better stimulate the proliferation of allogeneic T lymphocytes and kill more breast cancer cells (MDA-MB-231) in vitro. Day-3 DCs had the same function as the day-7 DCs, but with a shorter culture period. Our findings suggested that day-3 DCs fused with whole apoptotic breast cancer cells could elicit effective specific antitumor T cell responses in vitro and may be developed into a prospective candidate for adoptivet immunotherapy.