Viscum album L. extracts (VE) are applied as complementary
cancer therapeutics for more than one century. Extracts contain several compounds like mistletoe
lectins (ML) 1-3 and viscotoxins, but also several minor ingredients. Since ML-1 has been described as one of the main active components harboring antitumor activity, purified native or recombinant ML-1 has been also used in clinical trials in the last years. The present study examined and compared the immunoboosting effects of three ML-1 containing drugs (the extract
ISCADOR Qu, the recombinant ML-1
Aviscumine, and purified native ML-1) in the context of the T-cell mediated killing of
glioma cells. Additionally we examined the possible underlying T-cell stimulating mechanisms. Using cocultures of immune and
glioma cells, a PCR-based microarray, quantitative RT-PCR, and an antibody-based array to measure
cytokines in blood serum, immunosupporting effects were determined. A highly aggressive, orthotopic, immunocompetent syngeneic mouse
glioma model was used to determine the survival of mice treated with
ISCADOR Qu alone or in combination with
tumor irradiation and
temozolomide (TMZ). Treatment of
glioblastoma (GBM) cells with
ISCADOR Qu that contains a high ML concentration, but also viscotoxins and other compounds, as well as with
Aviscumine or native ML-1, enhanced the expansion of
cancer cell-specific T-cells as well as T-cell-mediated
tumor cell lysis, but to a different degree. In GBM cells all three ML-1-containing preparations modulated the expression of immune response associated genes. In vivo, subcutaneous
ISCADOR Qu injections at increasing concentration induced
cytokine release in immunocompetent VM/Dk-mice. Finally,
ISCADOR Qu, if applied in combination with
tumor irradiation and TMZ, further prolonged the survival of
glioma mice. Our findings indicate that ML-1 containing drugs enhance
anti-GBM immune responses and work in synergy with
radiochemotherapy. Therefore, adjuvant mistletoe
therapy should be considered as an auspicious treatment option for
glioma patients.