Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model

Abstract 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.http://deepblue.lib.umich.edu/bitstream/2027.42/134739/1/12885_2016_Article_2982.pd

Nádorová imunoterapie založená na synergii agonistů TLR a ligandů stimulujících fagocytózu. Posouzení spoluúčasti získané imunity.

The aim of this thesis is to improve the therapeutic effect of the immunotherapy based on the synergy of TLR agonists with phagocytosis stimulating ligands. Furthermore, this thesis is focused on the information transfer to the specific immunity, as well as it pursues the study of the specific immunity relevance during cancer immunotherapy

Studium mechanismů nádorové imunoterapie založené na kombinaci resiquimodu s kotveným mananem a její další optimalizace

The aim of this thesis was to analyse the tumour infiltration, identify the content of the infiltrate and determine inflammatory cytokine IFN-gamma. We also studied the possibilities of strengthening immunotherapeutic effect