Most cited article - PubMed ID 11561867
Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57Bl6 mice with syngeneic melanoma B16
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.
- Keywords
- Cancer immunotherapy, Innate immunity, Mannan, Melanoma, Neutrophils, Phagocytosis, Resiquimod,
- MeSH
- Cytokines metabolism MeSH
- Phagocytosis MeSH
- Imidazoles pharmacology MeSH
- Immunotherapy * methods MeSH
- Neutrophil Infiltration immunology MeSH
- Ligands MeSH
- Mannans immunology MeSH
- Melanoma, Experimental MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Neoplasms immunology metabolism pathology therapy MeSH
- Neutrophils immunology metabolism MeSH
- Poly I-C immunology MeSH
- Immunity, Innate * MeSH
- Respiratory Burst immunology MeSH
- Toll-Like Receptors agonists metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cytokines MeSH
- Imidazoles MeSH
- Ligands MeSH
- Mannans MeSH
- Poly I-C MeSH
- resiquimod MeSH Browser
- Toll-Like Receptors MeSH
