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Modulatory Potency of the ß-Galactoside-specific Lectin from Mistletoe Extract (Iscador) on the Host Defense System in Vivo in Rabbits and Patients¹

Laboratory of Immunology, Lucas Clinic, CH-4144 Arlesheim, Switzerland [T. H., K. H.]; and the Max Planck Institute for Experimental Medicine, Department of Chemistry, Hermann-Rein-Strasse 3, D-3400 Göttingen, FRG [H-J. G.]

Proprietary extract of mistletoe (Iscador) that has federal approval for clinical application can exhibit immunomodulatory capacity. However, the nature of this responsible substance has still remained elusive. To validate the hypothesis that specific lectin-carbohydrate interactions at least participate in eliciting immunomodulation, the modulatory efficiency of the major ß-galactoside-specific mistletoe lectin (ML I) from the clinically applied extract on selected immunological parameters was monitored "in vivo" in rabbits. Injections of nontoxic doses of the purified lectin or even only of its carbohydrate-binding subunit (0.25–1.0 ng/kg) into rabbits yielded significant increases in natural killer cytotoxicity, frequency of large granular lymphocytes, and phagocytic activity of granulocytes. In the clinically relevant situation, changes in these parameters were also determined in cancer patients after extract (Iscador) injection s.c. as well as i.v., emphasizing the potential relevance of the lectin. Comparative analyses of the changes in the selected parameters following injection of extract with normal lectin content as well as of extract, selectively depleted of lectin, into healthy volunteers corroborated this inference. Lectin depletion by affinity chromatography was highly specific and did not affect any other substance in the extract. Remarkably, contamination by endotoxin has been rigorously excluded in each applied specimen. These results encourage detailed elucidation of lectin action on various parts of the tumor defense system "in vitro" with the long range goal of achieving progress in the treatment of cancer through immunological strategies, exploring selective mediatory lectin-carbohydrate interactions.

¹ This study was supported in part by a grant from the BMFT program on alternative methods for cancer therapy.

² To whom requests for reprints should be addressed, at Laboratory of Immunology, Lucas Clinic, CH-4144 Arlesheim, Switzerland.

Received 3/30/89. Accepted 5/26/89.

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