Cancer Immunology, Immunotherapy

, Volume 62, Issue 8, pp 1283–1292 | Cite as

Mistletoe lectin has a shiga toxin-like structure and should be combined with other Toll-like receptor ligands in cancer therapy

  • Claudia Maletzki
  • Michael Linnebacher
  • Rajkumar Savai
  • Uwe Hobohm
Opinion Paper


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.


Mistletoe extract Mistletoe lectin Pattern recognition receptor ligands Shiga toxin Cancer immunotherapy 


Conflict of interest

All authors declare that neither of us has a significant financial arrangement or affiliation with any product or services used or discussed in our paper, nor any potential bias against another product or service.

Animal experiment declaration

Animal experiments were performed in accordance with the German legislation on the protection of animals and the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Research Council; NIH Guide, vol. 25, No. 28, 1996). All animal experiments were approved by the local agency for animal welfare (Landesamt für Landwirtschaft, Lebensmittelsicherheit und Fischerei, Mecklenburg-Vorpommern).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Claudia Maletzki
    • 1
  • Michael Linnebacher
    • 1
  • Rajkumar Savai
    • 2
  • Uwe Hobohm
    • 3
  1. 1.University of RostockRostockGermany
  2. 2.Max Planck Institute for Heart and Lung ResearchBad NauheimGermany
  3. 3.University of Applied SciencesGiessenGermany

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