title: Mistletoe lectin has a shiga toxin-like structure and should be combined with other Toll-like receptor ligands in cancer therapy.
abstract: Mistletoe extract (ME) is applied as an adjuvant treatment in cancer therapy in thousands of patients each year in Europe. The main immunostimulating component of mistletoe extract, mistletoe lectin, recently has been shown to be a pattern recognition receptor ligand and hence is binding to an important class of pathogen-sensing receptors. Pattern recognition receptor ligands are potent activators of dendritic cells. This activation is a prerequisite for a full-blown T-cell response against cancer cells. Pattern recognition receptor ligands are increasingly recognized as important players in cancer immunotherapy. We collect evidence from case studies on spontaneous regression, from epidemiology, from experiments in a mouse cancer model, and from protein structure comparisons to argue that a combination of mistletoe therapy with other pattern recognition receptor ligand substances leads to an increased immune stimulatory effect. We show that mistletoe lectin is a plant protein of bacterial origin with a 3D structure very similar to shiga toxin from Shigella dysenteriae, which explains the remarkable immunogenicity of mistletoe lectin. Secondly, we show that a combination of pattern recognition receptor ligands applied metronomically in a cancer mouse model leads to complete remission, while single pattern recognition receptor ligands slowed tumor growth. Taken together, we propose to combine mistletoe drugs with other pattern recognition receptor ligand drugs to increase its efficacy in adjuvant or even primary cancer therapy.
authors.affiliation: University of Rostock, Rostock, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Maletzki
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebacher
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Savai
authors.forename: Uwe
authors.initials: U
authors.lastname: Hobohm
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005408:Flagellin / Q000008:administration & dosage; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D014784:Mistletoe / Q000378:metabolism*; D008958:Models, Molecular; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008517:Phytotherapy; D037121:Plant Lectins / Q000008:administration & dosage / Q000737:chemistry*; D011487:Protein Conformation; D022621:Shiga Toxin / Q000737:chemistry; D013997:Time Factors; D051193:Toll-Like Receptors / Q000819:agonists*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D007093:Imidazoles; D008070:Lipopolysaccharides; D037121:Plant Lectins; D051193:Toll-Like Receptors; D005408:Flagellin; D022621:Shiga Toxin; C402365:resiquimod