Immundefizienz bei Patienten mit Kopf- Hals- Plattenepithelkarzinomen: Eine rationale Grundlage für den adjuvanten Einsatz des Immunmodulators ML

Journal/Book: Otorhinolaryngol Nova 4, 152-159. 1994;

Abstract: In spite of progress in surgical and radiological techniques, it hashardly been possible to improve the 5-year survival rate in patientswith squamous cell carcinomas in the head and neck area (HNSCC) duringthe past 20 years. The application of adjuvant or neo-adjuvantchemotherapy is still being discussed controversially and in moststudies it has not resulted in any prolongation of survival time. Theincidence of SCC in the mouth and pharynx has increased continuously inthe last 20 years. At present HNSCC has an incidence of 6% worldwide andholds the 6th place among all cancer diseases. By the present state ofinternational knowledge the 5-year survival time of HNSCC can only beimproved by an adequate adjuvant therapy concept of tumour-immunologicalcompetence, because all standard therapy regimes have animmunosuppressive effect upon the already present immunodeficientcondition. Essential reactions within the inter- and intracellularbiosignalling system, and thus also in the immune system, are mediatedby lectin-carbohydrate interactions. It could be demonstrated in basicstudies and cell cultures, as well as in animal experiments and in humanbeings, that the main mistletoe lectin ML-1 had a dose-dependentimmunomodulating, that is an immunosuppressing or -stimulating, effect.ML-1 could be purified by affinity and gel filtration chromatography andwas characterized by electrophoretic methods and by gas chromatography.As an optimal dosage for immunostimulation 1 ng/kg body weight wasdetermined. In 1990 an aqueous extract from popular mistletoe(Eurixorregistered trade mark) was approved by the Bundesgesundheitsamt,which, in contrast to the other preparations on the pharmaceuticalmarket, contains a standardized amount of mistletoe lectin ML-1. Itcould be shown in vitro that ML-1 binds sugar specifically atlymphocytes and monocytes which results in an enhanced phosphorylationof the 28-kD protein (T lymphocyte receptor) and thephosphatidyl-4,5-biphosphate. ML-1 also induces a rise in free availablecalcium and a significant expression of interleukin (IL)-2 and HLA-DQreceptor as a correlate to the T and B lymphocyte activation. It causesa strong liberation of cytokines by mononuclear cells of immune response(IL-1, IL-2, interferon-gamma, tumour necrosis factor alpha) and has noinfluence on the rate of proliferation of human and murine tumour cells.The number of lung and liver metastases could be reduced significantlyin two in vivo murine tumour models, in which subcutaneous ML-1injections were applied. So far, no prospective controlled study exists,evaluating the effect of ML-1 in a defined tumour on the crucialcriteria in oncology, e.g. the effect on survival time, recurrence rateor life quality. Within the scoop of a prospective and randomizedmulticentred study this course is followed for the first time, as onlythe result of extensive clinical studies can set the standard for arealistic assessment of an antitumour effect in patients.

Keyword(s): Medical:squamous-cell-carcinoma /drug therapy

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Immundefizienz bei Patienten mit Kopf- Hals- Plattenepithelkarzinomen: Eine rationale Grundlage für den adjuvanten Einsatz des Immunmodulators ML - I