Inhibition and promotion of tumor growth with adeno-associated virus carcinoembryonic antigen vaccine and Toll like receptor agonists
| Autor: | Selvarangan Ponnazhagan, Pierre L. Triozzi, Wayne Aldrich |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Myeloid endocrine system diseases viruses regulatory T cells Mice 0302 clinical medicine Carcinoembryonic antigen IL-2 receptor 0303 health sciences Toll-like receptor Vaccines Synthetic Imiquimod Membrane Glycoproteins Thelper cells myeloid suppressor cells T-Lymphocytes Helper-Inducer Dependovirus 3. Good health medicine.anatomical_structure Oligodeoxyribonucleotides 030220 oncology & carcinogenesis Colonic Neoplasms Aminoquinolines Molecular Medicine Female Mice Transgenic toll like receptors Biology Cancer Vaccines Article Viral vector 03 medical and health sciences Immune system Cell Line Tumor medicine Animals Humans dendritic cells Molecular Biology neoplasms 030304 developmental biology Cell Proliferation TLR9 TLR7 digestive system diseases Carcinoembryonic Antigen Mice Inbred C57BL Gene Expression Regulation Toll-Like Receptor 7 Toll-Like Receptor 9 Immunology biology.protein |
| Zdroj: | Cancer gene therapy |
| ISSN: | 1476-5500 0929-1903 |
| Popis: | Carcinoembryonic antigen (CEA) is a cancer vaccines' target. Several features of recombinant adeno-associated virus (rAAV) are attractive for vaccine applications. Combining other viral vector vaccines with Toll-like receptor (TLR) agonists enhances antitumor immunity. Wild-type and CEA transgenic (Tg) mice were immunized with rAAV-expressing CEA, the TLR9 agonist, oligodinucleotide (ODN)1826 and the TLR7 agonist, imiquimod. Mice were challenged with MC38 colon tumor cells and MC38 cells expressing CEA. rAAV-CEA immunization combined with ODN1826 or imiquimod enhanced CEA-specific T-helper 1 immunity and protected against tumor challenge in wild-type but not in CEA-Tg mice. In contrast, immunization with rAAV-CEA in CEA-Tg mice could abrogate the antitumor effects of ODN1826 and promote tumor growth. Compared to wild-type, CEA-Tg mice were characterized by a greater myeloid suppressor cell and T-helper 2 response to TLR agonists and to syngeneic tumors. Depleting PDCA1(+) plasmacytoid dendritic cells and Gr1(+) myeloid cells increased anti-CEA immune responses in CEA-Tg mice to rAAV-CEA-ODN1826 immunization, whereas depleting CD25(+) T cells did not. There are differences in the response of wild-type and CEA-Tg mice to rAAV-CEA, TLR agonists and syngeneic tumor. In CEA-Tg mice, tumor growth can be promoted with rAAV-CEA and TLR agonists. Dendritic and myeloid cells play a regulatory role. |
| Databáze: | OpenAIRE |
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