Investigation of the possibility of the reduction of chemotherapeutics by activation of PBMCs in tumor cell

The three big columns in the treatment of malignant tumour are chemotherapeutics, radiotherapy and surgical interventions. However, beside these three types of therapies the hormone therapy plays an extremely important role as well. In modern medicine chemotherapeutics are the main therapy for most malignant tumour diseases. This fact mainly follows from the absence of other, just as well working alternatives. Administration of these substances sometimes leads to strong undesirable side effects or to insufficient response. The mentioned lack of alternatives, neither in the form of chemotherapeutics nor in the form of other possibilities of treatment, can heavily endanger the desired therapy success. Today it is clear that there is a complicated teamwork between immune defence, inflammation and carcinoma. Up to twenty times more Macrophages are located in tumour surroundings than in healthy fabric. These so called tumour associated or M2 Macrophages (TAMs) differ from other Macrophages, the M1 Macrophages, by their non-inflammatory effects. They do not necessarily lead to immune defence. In 2008, Hunder et al described in a study that cloned CD4+ T cells injected in Melanoma lead to a remission of the tumour. An activation of PBMCs and subsequent administration could be helpful with the fight against malignant tumours. Using the Δ;NS virus PBMCs will be stimulated - more exactly, monocytes and as a result PBMCs - and initiate an immunological reaction against tumour cells. Furthermore it will be shown that PBMCs immunosuppressed earlier - as they appear in tumour surroundings - can be activated by means of Δ;NS virus again. The 'tumour friendly' environment may be altered in a 'tumour-unfriendly' environment, and, as a direct consequence, the growth of the tumour cells will decrease. It is clear that this activation of the immune system cannot substitute a chemotherapy as a whole, but an improved killing or reduction of the dose should lead to the reduction of the side effects. Till present the effect of ineffective or insufficiently effective chemotherapy could be increased and their application could also be possible for tumour forms resistant to therapy. In this study co-cultures with human tumour cell lines and human PBMCs were used. The PBMCs were divided into two parts, one was activated by means of Δ;NS virus, the other remained untreated. They were separated into activated and not activated groups of PBMCs and pipetted on tumour cells (Target cells). Afterwards different concentrations of chemotherapeutics were added. In the second test arrangement only the supernatant was used by activated and not activated PBMCs and its effects with and without chemotherapy on Target cells were observed. After an agreed period the survival of the target cells was measured by means of EZ4u. The substrate is metabolised by mitochondria and the colour envelope is clearly visible. This colour envelope was measured photometrically to receive exact values of calculations. MCF-7 and Panc-I cells were used. The test procedure ELISA was used to the proof of TNF-α in the supernatant and to deliver more exact explanations about the activation of the PBMCs. (INIS)