Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model
| Autor: | Ivana Jochmanova, Andra Vieru, Jindřich Chmelař, Veronika Caisova, Simona Glaserová, Nikol Vácová, Lucie Paďouková, Jan Kopecký, Gabriela Krejčová, Zuzana Kumžáková, Hana Husníková, Katherine I. Wolf, Jan Ženka |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Cancer Research Neutrophils medicine.medical_treatment Melanoma Experimental Monophosphoryl Lipid A Cancer immunotherapy Ligands Mannans chemistry.chemical_compound Mice 0302 clinical medicine Neoplasms Receptor Melanoma Respiratory Burst Innate immunity Toll-Like Receptors Imidazoles Mannan Neutrophil Infiltration Oncology 030220 oncology & carcinogenesis Cytokines Female Immunotherapy Resiquimod Research Article Agonist medicine.drug_class Phagocytosis 03 medical and health sciences medicine Genetics Animals Innate immune system business.industry medicine.disease Immunity Innate Disease Models Animal 030104 developmental biology Poly I-C chemistry Immunology Cancer research business |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-016-2982-x |
| Popis: | Background Using killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19th century. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans. Methods B16-F10 murine melanoma model was used. For the stimulation of phagocytosis, mannan or N-formyl-methionyl-leucyl-phenylalanine, was covalently bound to tumor cells or attached using hydrophobic anchor. The following agonists of Toll-like receptors were studied: monophosphoryl lipid A (MPLA), imiquimod (R-837), resiquimod (R-848), poly(I:C), and heat killed Listeria monocytogenes. Results R-848 proved to be the most suitable Toll-like receptor agonist for our novel immunotherapeutic approach. In combination with covalently bound mannan, R-848 significantly reduced tumor growth. Adding poly(I:C) and L. monocytogenes resulted in complete recovery in 83% of mice and in their protection from the re-transplantation of melanoma cells. Conclusion An efficient cancer treatment results from the combination of Toll-like receptor agonists and phagocytosis stimulating ligands bound to the tumor cells. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2982-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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