The use of anchored agonists of phagocytic receptors for cancer immunotherapy: B16-F10 murine melanoma model.

Abstract

The application of the phagocytic receptor agonists in cancer immunotherapy was studied. Agonists (laminarin, molecules with terminal mannose, N-Formyl-methioninyl-leucyl-phenylalanine) were firmly anchored to the tumor cell surface. When particular agonists of phagocytic receptors were used together with LPS (Toll-like receptor agonist), high synergy causing tumour shrinkage and a temporary or permanent disappearance was observed. Methods of anchoring phagocytic receptor agonists (charge interactions, anchoring based on hydrophobic chains, covalent bonds) and various regimes of phagocytic agonist/LPS mixture applications were tested to achieve maximum therapeutic effect. Combinations of mannan/LPS and f-MLF/LPS (hydrophobic anchors) in appropriate (pulse) regimes resulted in an 80% and 60% recovery for mice, respectively. We propose that substantial synergy between agonists of phagocytic and Toll-like receptors (TLR) is based on two events. The TLR ligand induces early and massive inflammatory infiltration of tumors. The effect of this cell infiltrate is directed towards tumor cells, bearing agonists of phagocytic receptors on their surface. The result of these processes was effective killing of tumor cells. This novel approach represents exploitation of innate immunity mechanisms for treating cancer.

• Authors: Tereza Janotová, Marie Jalovecká, Marie Auerová, Ivana Švecová, Pavlína Bruzlová, Veronika Maierová, Zuzana Kumžáková, Štěpánka Cunátová, Zuzana Vlčková, Veronika Caisová, Petra Rozsypalová, Katarína Lukáčová, Nikol Vácová, Markéta Wachtlová, Jiří Salát, Jaroslava Lieskovská, Jan Kopecký, Jan Ženka
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e85222 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24454822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Glucans
• Ligands
• Lipopolysaccharides
• Polysaccharides
• Receptors, Immunologic
• Toll-Like Receptors
• phagocytosis receptor
• laminaran
• Mannose

Topics

• Animals
• Cell Proliferation (drug effects)
• Cytokines (metabolism)
• Disease Models, Animal
• Flow Cytometry
• Glucans
• Immunotherapy
• Ligands
• Lipopolysaccharides (pharmacology)
• Macrophage Activation (drug effects)
• Mannose (chemistry)
• Melanoma, Experimental (drug therapy, immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Polysaccharides (pharmacology, therapeutic use)
• Receptors, Immunologic (agonists, metabolism)
• Signal Transduction (drug effects)
• Survival Analysis
• Toll-Like Receptors (metabolism)