The use of anchored agonists of phagocytic receptors for cancer immunotherapy: B16-F10 murine melanoma model.
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.
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Tereza
T
Janotová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Marie
M
Jalovecká
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Marie
M
Auerová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Ivana
I
Švecová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Pavlína
P
Bruzlová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Veronika
V
Maierová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Zuzana
Z
Kumžáková
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Štěpánka
Š
Cunátová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Zuzana
Z
Vlčková
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Veronika
V
Caisová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Petra
P
Rozsypalová
Department of Pathology, Regional Hospital, České Budějovice, Czech Republic.
Katarína
K
Lukáčová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Nikol
N
Vácová
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Markéta
M
Wachtlová
Department of Virology, Veterinary Research Institute, Brno, Czech Republic.
Jiří
J
Salát
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Jaroslava
J
Lieskovská
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Jan
J
Kopecký
Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Jan
J
Ženka
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005936:Glucans; D007167:Immunotherapy; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008358:Mannose / Q000737:chemistry; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use; D011971:Receptors, Immunologic / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D051193:Toll-Like Receptors / Q000378:metabolism
D016207:Cytokines; D005936:Glucans; D008024:Ligands; D008070:Lipopolysaccharides; D011134:Polysaccharides; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; C028495:phagocytosis receptor; C008247:laminaran; D008358:Mannose