PloS one, 2014-07, Vol.9 (7), p.e101854-e101854
2014
Details
- Autor(en) / Beteiligte
- Titel
- Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models
- Ist Teil von
- PloS one, 2014-07, Vol.9 (7), p.e101854-e101854
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0101854Titel-ID: cdi_plos_journals_1544513071
- Format
- –
- Schlagworte
- Analysis, Animal models, Animals, Antibodies, Anticancer properties, Antigen (tumor-associated), Antigens, Antigens, Neoplasm - genetics, Antigens, Neoplasm - immunology, Antigens, Neoplasm - metabolism, Biocompatibility, Biology and Life Sciences, Cancer therapies, Cancer vaccines, Cancer Vaccines - immunology, CD11c antigen, CD4 antigen, CD40 Ligand - genetics, CD40 Ligand - immunology, CD40 Ligand - metabolism, CD40L protein, Cell survival, Chemotherapy, Clinical trials, Colony-stimulating factor, Colorectal cancer, Colorectal carcinoma, Cytotoxicity, Dendritic cells, Deoxyribonucleic acid, DNA, DNA vaccines, Drug dosages, Engineering schools, Female, Genes, Granulocyte-macrophage colony-stimulating factor, Granulocyte-Macrophage Colony-Stimulating Factor - genetics, Granulocyte-Macrophage Colony-Stimulating Factor - immunology, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism, Granulocytes, Haplotypes, Histocompatibility antigens, HLA antigens, HLA histocompatibility antigens, House mouse, Immunity, In vivo methods and tests, Infiltration, Injections, Intraperitoneal, Liver, Lungs, Lymph nodes, Lymphocytes, Lymphocytes T, Macrophages, Major histocompatibility complex, Medicine and Health Sciences, Melanoma, Metastases, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Micelles, Natural killer cells, Oncology, Pancreatic cancer, Peptides, Peritoneum, Physiology, Plasmids, Rejection, Research and Analysis Methods, RNA-Binding Proteins - genetics, RNA-Binding Proteins - immunology, RNA-Binding Proteins - metabolism, Spleen, Squamous cell carcinoma, Surgery, T cells, Tumors, Vaccines, Vectors (Biology)