Zeitschrift für Phytotherapie 2012; 33 - P14
DOI: 10.1055/s-0032-1313254

Difficulties and perspectives of immunomodulatory therapy with mistletoe lectins and standardized mistletoe extracts in evidence based medicine

T Hajto 1, K Fodor 2, P Perjési 2, P Németh 1
  • 1Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Hungary
  • 2Department of Medical Chemistry, University of Pécs, Faculty of Medicine, Hungary

Aqueous extracts of the mistletoe plant (ME) have been used for a long time as complementary medicine with immunomodulatory effects in tumor therapy. However, the immunological efficacy of various ME preparations can differ considerably from each other. The immunomodulatory effect of ME therapy is based on lectin – sugar interactions in the cell membrane of the innate immune system. A selective binding of mistletoe lectins (ML) on CD75 ganglioside receptors of IL-12 producing macrophages and dendritic cells can play an important role as well. The positive effects of ME on immune system correlate with the lectin activity shown a bell shaped dose-response curve. Preclinical investigations in tumor models (using nude mice xenotransplanted with human leiomyosarcoma and IL-12 deficient C57BL6 mice) show that without immunological activity by ME there is less anti-tumor efficacy. Therefore a correct determination of mistletoe lectins for a standardization of commercial ME is essential, hut difficult since plant mistletoe lectins exhibit heterogeneity resulting most likely from the posttransiational processing. In addition, amino acid analysis of ML revealed numerous conservative substitutions along their amino acid sequence.

Successful immunotherapeutic interventions by ML and ME must be associated with a lectin-induced improvement of balance of the innate immunity in the tumor microenvironment. An optimized, standardized immunological application of ML and ME may be helpful in enhancing the quality and prolongation of life. Mistletoe lectins and their fragments may be important candidates for an immunotherapy with targeting strategy. Further pharmacochemical research is required to introduce appropriate standardization procedures allowing better reproducibility for mistletoe preparations.