From Ill-Defined Extracts to the Immunomodulatory Lectin: Will There be a Reason for Oncological Application of Mistletoe?*

Abstract

There is an obvious discrepancy between the popularity of mistletoe extracts and their classification as a non-conventional treatment modality with unproven efficacy in oncology. The commercial preparations suffer from several major drawbacks: lack of precise declarations for the molecular characteristics and the concentrations of diverse extract constituents; the composition of extracts can even be influenced by the different methods of preparation, the time of harvest, and the type of host tree; lack of experimentally substantiated instructions for the dose of supposedly effective substance(s) and the schedule of applications to clinically trigger an undisputably documented antitumoral activity; lack of thorough clinical studies according to the generally accepted criteria as the measure for responsible recommendations. To provide the indispensable set of data for a rational decision, the immunomodulatory galactosidespecific lectin was biochemically characterized and its antitumoral/antimetastatic activity was documented in three murine tumor model systems, occurring within a narrow dose range. Biweekly treatment with s.c. injections of a lectin dose of 1 ng/kg caused no notable harmful side-effects in patients, who showed modulation of selected immune parameters. In a group of 23 patients with advanced cancer no at least partial remission was seen. In principle, enhancement of factors like cytokine availability or NK-cell activity is not necessarily linked to therapeutic benefit. Factors such as growth promotion of certain tumor cell lines by cytokines, occurrence of respective insensitivity in advanced stages or varying levels of target sensitivity to cell-mediated cytotoxicity with significant interindividual differences deserve attention. Each tumor class has to be considered separately for its responsiveness. Similarly crucial for the decision of the focus of trials are valid suggestions for indicators to reliably recognize responders. Monitoring, for example, the presence of cytokine receptors or of MHC epitopes on tumor cells or the stimulation of the levels of acute-phase proteins in serum may be helpful. Taken together, this generally applicable course of research for a rigorously defined plant preparation or an isolated compound, culminating in the decisive clinical trials according to the approved criteria, will help answer the pertinent question on the oncological relevance of this treatment modality.

Targeting carbohydrates: a novel paradigm for fungal control

“…The specific changes which take place in the oligosaccharide profile that project outwards from the code surface as part of glycoprotein or glycolipid conjugates are known to occur in cancer, when a non-malignant cell turns to malignant, as well as in other diseases, justify the use of lectins as diagnostic probes. Seven different types of mistletoe extracts are commercially available with variable anticancer effects (Gabius et al 1994), due to the antitumour cytotoxicity effects of their lectins. Research in tumour lectinology is gaining a strong impetus as lectins became increasingly used in cancer therapy.…”

Phytotherapeutic Immunomodulation as a Treatment Modality in Oncology: Lessons from Research with Mistletoe

“…This reaction is strictly dependent on recognitive protein-sugar interaction, as shown in respective controls (49). By altering mediator levels in the complex cytokine network, the lectin can rightfully be denoted as "biological response modifier" (50,51). Current strides in unveiling the uncertainty of such endogenous mediators are welcome sparks to ignite efforts to clarify the role of altered cytokine availability to exclude any potential harm for the patients.…”

Ligaria cuneifolia flavonoid fractions modulate cell growth of normal lymphocytes and tumor cells as well as multidrug resistant cells

“…A single galactoside lectin was isolated but it only partially resembles the immunomodulatory effects found for the whole extract (Ferna´ndez et al, 2003). In contrast, the lectins from V. album are the most active components of European mistletoe preparations and are potent apoptosis inducers (Gabius et al, 1992(Gabius et al, , 1994Hajto et al, 1997;Hostanska et al, 1996/97).…”