Evaluation of the supportive treatment with RES-IMMun in 30 patients with advanced tumours.
Klinik für Tumorbiologie, Freiburg
Most patients with tumour diseases also utilize apply unconventional treatment methods (UTM) of cancer medicine in addition to the conventional therapeutics. In their preamble the clinic for tumour biology has therefore set itself the goal to accompany patients with tumour diseases who apply UTM clinically and to evaluate the therapeutic significance and the possible potential for adverse side effects of the respective UTM by means of e.g. clinical studies, observational studies or assessments. RES-IMMUN® is the successor product of RESISTOZELL® and is utilized mainly by numerous naturopathically working physicians and practitioners to primarily strengthen the general health condition and for the sole or additional therapy of patients with tumour diseases. Oncological expert groups have assigned RES-IMMUN® to UTMs. Despite numerous positive case studies no extensive, critical or independent evaluation of immune modulators existed. Therefore within the RESI project about 20 patients with tumour diseases who received RES-IMMUN® from their physicians with a naturopathic orientation were or are examined clinically and the course of the disease and the tolerability are documented.
Project start: 1st quarter 2014
Assessment of the influence of cytostatics on the proliferation, survival and immune competence of tissue macrophages
Centre for Biological Signaling Studies, Universität Freiburg
Chemotherapy is still a standard treatment in current cancer treatment. It was developed on the basis of the increased rate of division and the decreased repair ability of tumour cells. The idea is to damage strongly proliferating tumour cells directly while leaving non-transformed cells of patients intact. However, all cytostatics, to different extents, have toxic effects on healthy cells, especially those which divide quickly such as cells of the hair follicle, the mucosal cells of mouth or gastro-intestinal tract. Unfortunately many immune cells also divide fast so that chemotherapy can lead to a lack of immune cells in the blood. This results in an elevated susceptibility to infections. In this context new research which shows that some chemotherapeutics damage not only cancerous cells but activate also the immune reply is of interest the Therefore, within this research project the influence of different chemotherapeutics on the proliferation, the overall survival and the activation of tissue macrophages as important immune cells shall be assessed. The resulting findings serve the optimization of oncological therapies and the protection of undesirable side effects.
Project start: 2nd quarter 2014
Development of therapy options directed at mast cells for the systemic mast cell activation disease as contribution to health promotion (Phase I)
Förderclub Mastzellforschung Gemeinnütziger e.V., Meckenheim;
Institut für Biochemie und Molekularbiologie, RWTH Aachen;
Institut für Humangenetik, Universität Bonn
Systemic mast cell activation disease (MCAD) defines a group of diseases which includes systemic mastocytosis, the mast cell activation syndrome and mast cell leukaemia. MCAD leads to an uncontrolled release of mast cell messenger compounds into all organs and tissues which can induce diffuse clinical ailments in different intensities. The symptoms range from fibromyalgic rheumatic complaints to irritable bowel syndrome.
With a frequency of 5- 17% MCAD is a common disease in physician’s routine. To date no explicit disease specific clinical marker exists. Treatment of the disease remains mainly symptomatic. Despite individual treatment adaptations no satisfactory treatment success is brought about in disabling MCAD with severe symptoms.
Within the project SYMCAD I supported together with the Förderclub Mastzellforschung e.V new findings shall be gained which in medium term shall lead to a more precise diagnosis and to individualised treatment. Because of the high number of affected persons the research plans are of great health-medical relevance and of socio-economic interest.
Project start: 3rd quarter 2015
Mass spectrometry analysis of the phosphoproteome of mast cell leukemia cells: curative effects of tyrosine kinase and MEK inhibitors
Proteomics Facility, IZKF Aachen,
Uniklinikum RWTH Aachen
The development of malignant tumours is based on numerous exogenous and endogenous factors. These can lead to changes in the activity of regulatory genes due to point mutations or cytogenetic aberrations. These in turn cause the activation or inhibition of intracellular signalling pathways which affect the growth behaviour of tumour cells directly or indirectly.
The focus of this research work is the tyrosine kinase KIT (c-Kit). It is a protein which is found in the cell membrane of various body cells and belongs to the class of receptor tyrosine kinases. Physiologically c-Kit is activated by the ligand stem cell factor (SCF) and affects the maturation and proliferation of healthy cells, especially of the haematopoietic systems. If mutated, c-Kit is persistently falsely activated and lead to various tumour diseases such as leukaemia, lymphoma, germ cell tumours, but also mast cell leukaemia.
The project will assess the different mast cell leukaemia cell lines for their phosphorylation properties. These lines differ both in their c-Kit mutation patterns as well as with regards to their proliferation and activation behaviour. As part of the work it will be assessed whether the phenotypic characteristics can be depicted in the activation pattern at the level of protein phosphorylation and which affect different pharmacologic inhibitors have on protein and cell activation. In the medium term the investigations shall synergistically serve to improve the targeted and dose reduced application of inhibitory compounds as well as their anti-tumour efficacy and the side effect profile and thus spare the health maintaining body resources.
Phase I study on combined immune therapy of patients with glioblastoma multiforme with NDV (new castle disease virus) and NDV-lysed tumour lysate loaded dendritic cells.
Immunologisches Onkologisches Zentrum Köln (IOZK);
Firma Biotissue AG, Freiburg
Mast cell-associated diseases: modification of the activity of murine mast cells by defined ingredients
Institut für Biochemie und molekulare Immunologie, Universitätsklinikum RWTH Aachen
The findings of SYMCAD I will contribute to treating mast cell activation disease (MCAD) more effectively and with less side-effects in the future. MCAD is a genetically determined malfunction of the mast cells. The range of symptoms includes diffuse as well as organ specific complaints e.g. in the gastrointestinal tract and in the muscles or joints and the connective tissue. Mast cells occur in nearly all body tissues and act there as very effective immunologic early warning system which is able to regulate the immune response. Mast cells recognise infiltrating pathogens such as viruses and bacteria, but also foreign compounds and various poisons at the outer border of the body, preferentially in mucosas. Depending on the respective danger they are able to initiate an appropriate immune response. However, malfunctioning of mast cells can lead to life-threatening, excessive reactions such as allergic asthma attacks or allergic shock. Then mast cells not only release the contents of their vesicles in an uncontrolled manner and in a short time but also large amounts of inflammatory signalling molecules. To date only a few active compounds exist which are able to counteract the chronic malfunctioning of mast cells long-term and with few side-effects. Within the clinically oriented research project SYMCAD I it could be shown in vitro that some medicines and signalling molecules can selectively affect crucial aspects, such as the activity of murine mast cells as well as their degree of de-granulation
Mast cell-associated diseases: differential analyses of the transcriptome within endotoxin tolerance in mast cells.
Institut für Biochemie und molekulare Immunologie, RWTH Aachen
The task of immune cells is to protect our body from pathogens. Persistent stimulation or repetitive stimulation in short spaces of time of macrophages (immune cells) with bacteria or their (endo-)toxins can lead to decreased activity of these immune cells. This condition is also described as endotoxin tolerance (ET) and is of great clinical and medical health importance. If, for example, a primary bacterial infection is followed by a secondary, ET immune cells are not able any more to react appropriately and to protect the body. Macrophages which are found in tumour tissues, but do not show anti-tumour activity appear to show comparable activity patterns, like ET macrophages.
The investigated mechanisms of ET are manifold and can affect different aspects (the LPS receptor, different cytoplasmic signal systems as well as nuclear transcriptional events). However, the question arises whether the findings on ET macrophages can be transferred to other ET cells such as e.g. mast cells.
Within the research project on the reaction of mast cells on the stimulation with different endotoxins we could already show that mast cells develop an ET and that this leads to a reduced inflammation inducing reaction. Furthermore, we could already depict the suppression of differential signalling pathways. The project SYMCAD II will evaluate whether only a general suppression of inflammation reaction occurs or whether also unique genes which play a non-inflammatory role in the immune response are specifically activated.
IBAN: DE91 6809 0000 0038 2290 01