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Analysis of the influence of selected chemotherapeutic agents on the effectiveness of anti-CD20 immunotherapy in B-cell neoplasms

Project Title
Analiza wpływu wybranych chemioterapeutyków na skuteczność immunoterapii anty-CD20 w nowotworach wywodzących się z limfocytów B.
Financing Institution
Lead
Nina Barbara Miązek
Project Objective

Non-Hodgkin's lymphomas account for about 2% of all malignant neoplasms in Poland, and their incidence has been systematically increasing in recent decades. Despite the wide availability of various forms of treatment, patients' response to therapy is not satisfactory. A significant problem is the resistance of cancer cells to the drugs used. The PI3 / AKT pathway plays a key role in the development of resistance to chemotherapy. Literature data show that some of the chemotherapeutic agents used in lymphoproliferative diseases can activate AKT kin / e. The results of our research have shown that AK T kinase can, in turn, regulate the amount of the CD20 antigen - a target protein for therapeutic monoclonal antibodies also used in the treatment of lymphomas. Most of the treatment regimens currently used are based on combining chemotherapeutic agents with immunotherapy. Hence, the understanding of the interactions between these two groups of drugs is extremely important in the context of selecting the best possible combinations of these drugs. The scientific goal of the project is to investigate the influence of selected chemotherapeutic agents on the amount of CD20 antigen in cancer cells and on the effectiveness of therapeutic monoclonal antibodies directed against this molecule. We intend to carry out the experiments in models of established cell lines derived from B lymphocytes as well as on cells isolated from patients with hematological hyperplasia. The results of our research will make it possible to select chemotherapeutic agents, which could increase the effectiveness of aiUy-CD20 immunotherapy. This will make it possible to propose the most advantageous combination therapy regimens with the use of both groups of Icków [sic! - see Polish version]. In a broader perspective, our project will contribute to a better understanding of the mechanisms of secondary resistance to chemotherapeutic agents.