Case Reports of Sarcoma Patients with Optimized Lectin-Oriented Mistletoe Extract Therapy

Kirsch, Angelika; Hajtò, Tibor

doi:10.1089/acm.2010.0596

Cited by 16 publications

(12 citation statements)

References 22 publications

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“…These data, in line with the clinical findings in early clinical trials (15,17,19), support the potential of this plant-derived recombinant lectin I as an anticancer agent, particularly with regard to its combined use with immune checkpoint inhibitors or chemotherapeutics, as postulated in case reports and clinical investigations (22,33). Nevertheless, further studies to validate the present findings and assess the detailed mechanisms and clinical efficacy of aviscumine are warranted.…”

Section: Discussionsupporting

confidence: 85%

“…The measured changes in patient plasma cytokine levels (increased IL-1β, TNF-α and IFN-γ and decreased IL-6 and IL-10 levels) indicate the activation of NK and T cells (19). A very recent study revealed that lectin structures represent PAMPs and thereby activate the immune system via PRRs (21)(22)(23). By focusing on NK cells, the present study was able to demonstrate a reproducible stimulation of NK cell antitumor activity for a non-toxic concentration range of aviscumine (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that lectins represent pathogen-associated molecular patterns (PAMPs) and thereby activate pattern recognition receptors (PRRs) causing the activation of the immune system via type-I phagocytic cells (21,22). Müthing et al (23) found a preferential binding of lectin I to Neu5Aca2-6Galβ1-4GlcNAc epitopes, and glycosphingolipids were also described to be overexpressed in various tumors and associated with cellular stress induction, causing cytokine release.…”

Section: Introductionmentioning

confidence: 99%

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Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells

et al. 2017

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Abstract. Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress-inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium-51-release assays against K-562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers. Two effector-to-target cell ratios (12.5:1 and 25:1) were used by two independent investigators with a focus on the concentration-dependent effect (0.5 vs. 1 ng/ml aviscumine), reproducibility (first vs. second investigator) and the specificity of the effect by comparison to a heat-inactivated aliquot and interleukin 2 (IL-2) stimulation (10 ng/ml). The mediation of the effect via degranulation was demonstrated by flow cytometric analyses of CD107α expression. Statistics were performed with SPSS using Student's t-tests for normally distributed data. Aviscumine induced a significant and reproducible, concentration-dependent increase in NK cell cytotoxicity (n=22; P<0.01 for both concentrations and ratios), which was also demonstrated when administered in combination with IL-2 (n=12; 12.5:1 ratio, P<0.001; 25:1 ratio, P=0.025) and when compared with the heat-inactivated aliquots (n=12; 12.5:1, P= 0.004; 25:1 ratio, P= 0.007). The mediation of its effect via interferon γ degranulation was demonstrated by significantly enhanced CD107α expression (n=7; P=0.005). Taken together, the results indicate that aviscumine induced an increase in NK cell anticancer cytotoxicity. These results highlight its clinical potential as an immunostimulatory agent, particularly with regard to combined use with chemotherapeutics or immune checkpoint inhibitors. However, further studies are required.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells

et al. 2017

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“…It was found that ML molecules functioning as ligands for pattern recognition receptors of innate immune system and they are docked to appropriate ganglioside molecules (CD75) of natural immune cells [15]. Thereby ML is capable of having a positive effect on the disturbed immune balance of tumor patients and case reports show some clinical benefits [16][17][18]. The active (sugar-binding) lectin content of commercially available IscadorR M special preparations is regularly measured by an optimized ELLA technique as published previously [9].…”

Section: Discussionmentioning

confidence: 99%

Improvement of Quality of Life in Tumor Patients after an Immunomodulatory Treatment with Standardized Mistletoe Lectin and Arabinoxylan Plant Extracts

Hajtò¹,

Horváth²,

Papp³

2016

Int J Neurorehabilitation Eng

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Background: In the last decades a special attention has been focused on the role of disturbed immune balance in the behavioral co-morbidities of tumor patients. The prognostic significance of malignant tumor-induced imbalance in the innate immune system is well known. The innate system uses a limited number of Pattern Recognition Receptors (PRR) to recognize conserved Pathogenic Associated Molecular Pattern (PAMP) structures expressed by microbes but not by host. Growing experiences suggest that the improvement of tumor induced disturbance of immune balance by using standardized plant PAMP like preparations goes often together with a better quality of life (QoL).

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“…Mistletoe is grown on different host trees such apple, pine, oak, fur, maple, poplar, or hawthorn. 23 In Europe, mistletoe lectin has been widely used as a complementary cancer drug for various cancers, such as gliomas, 24 acute lymphoblastic leukemia, 25 breast cancer, 26 sarcoma, 27 and others. 28 However, there has been no study showing the anticancer activity of mistletoe alkali.…”

Section: Ge Effects Of Mistletoe Alkali On Human Osteosarcoma Cells (mentioning

confidence: 99%

Proliferation, Apoptosis, and Invasion Effects of Mistletoe Alkali on Human Osteosarcoma U2OS In Vitro

Wang

Pang

et al. 2016

International Surgery

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The objective of this study was to evaluate the effects of mistletoe alkali on human osteosarcoma cells (U2OS) in vitro. Osteosarcoma is the most common primary malignant bone tumor; although there are a lot of therapies such as surgery, radiotherapy, and chemotherapy, its prognosis is still very poor. There is increasing interest in the protective biological function of natural antioxidants contained in Chinese medicinal herbs, which are candidates for the prevention of tumors. Mistletoe alkali is one of the compounds extracted from Viscum coloratum (Komar.) Nakai, one kind of mistletoe, whose extracts contribute to the improvement of the prognosis of patients with malignancies. The effect of mistletoe alkali on the growth of U2OS cells was compared with 5-fluorouracil (5-FU), using a cell counting kit-8 (CCK-8). The influence of mistletoe alkali on U2OS's proliferation and apoptosis was tested by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling staining and immunocytochemical staining of caspase 3 and proliferating cell nuclear antigen. Additionally, the invasion ability of U2OS cells was detected using a Boyden chamber transwell migration assay. CCK-8 assays gave an IC50 of 7 μg/mL for mistletoe alkali. Compared with 5-FU, mistletoe alkali inhibited U2OS proliferation and induced apoptosis more effectively. The invasion ability of U2OS was also weaker in mistletoe alkali than in 5-FU. Mistletoe alkali significantly inhibited growth and invasion abilities of U2OS cells and induced their apoptosis in vitro. Mistletoe alkali may be a more effective drug for human osteosarcoma than the standard chemotherapeutic drug 5-FU.

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Case Reports of Sarcoma Patients with Optimized Lectin-Oriented Mistletoe Extract Therapy

Abstract: It seems that this disease is beneficially influenced by optimized lectin-oriented ME therapy since patients with sarcoma may react especially well to the improved balance of natural immunological mechanisms. These case reports require further clinical studies with patients with sarcoma.

Cited by 16 publications

References 22 publications

Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells

Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells

Improvement of Quality of Life in Tumor Patients after an Immunomodulatory Treatment with Standardized Mistletoe Lectin and Arabinoxylan Plant Extracts

Proliferation, Apoptosis, and Invasion Effects of Mistletoe Alkali on Human Osteosarcoma U2OS In Vitro

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