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

Autor: Jan Ženka, Tereza Janotová, Veronika Caisova, Markéta Wachtlová, Štěpánka Čunátová, Katarína Lukáčová, Zuzana Vlčková, Veronika Maierová, Ivana Švecová, Marie Auerová, Jaroslava Lieskovská, Nikol Vácová, Jan Kopecký, Jiří Salát, Petra Rozsypalová, Marie Jalovecka, Zuzana Kumžáková, Pavlína Bruzlová
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Lipopolysaccharides
Melanomas
Skin Neoplasms
Mouse
medicine.medical_treatment
Melanoma
Experimental
Cancer Treatment
lcsh:Medicine
Ligands
Biochemistry
Mice
Cancer immunotherapy
Drug Discovery
Basic Cancer Research
Receptors
Immunologic
Receptor
lcsh:Science
Glucans
Skin Tumors
Multidisciplinary
Malignant Melanoma
Toll-Like Receptors
Animal Models
Flow Cytometry
Innate Immunity
Oncology
Cytokines
Medicine
Immunotherapy
medicine.symptom
Signal transduction
Signal Transduction
Research Article
Biotechnology
Agonist
Drugs and Devices
Drug Research and Development
medicine.drug_class
Inflammation
Malignant Skin Neoplasms
Dermatology
Biology
Model Organisms
Polysaccharides
medicine
Animals
Cell Proliferation
Immune Evasion
Innate immune system
Cell growth
lcsh:R
Immunity
Cancers and Neoplasms
Macrophage Activation
Survival Analysis
Mice
Inbred C57BL
Disease Models
Animal
Immunology
Cancer research
Clinical Immunology
lcsh:Q
Mannose
Zdroj: PLoS ONE, Vol 9, Iss 1, p e85222 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: