Foundation for Polish Science

In December 2016, the Medical University of Warsaw in consortium with Cellis Sp. z o.o., began the implementation of the project entitled: "Breakthrough cellular system of drug delivery to tumors" under the TEAM-TECH program of the Foundation for Polish Science, co-financed by the European Union from the European Regional Development Fund. The project manager is Dr Tomasz Rygiel from the Department of Immunology. The aim of the project is to develop a breakthrough method of drug delivery to tumors (including non-bleeding sites), directly to neoplastic cells. The project's innovation is based on the creation of a new, targeted drug delivery system to cancer cells, which is a kind of a "Trojan horse". The system is made up of three components: (1) living cells of the immune system that carry a charge of (2) protein "boxes" (naturally found in the body) "filled" (3) with an anti-cancer drug. Selected cells of the immune system have the natural ability to migrate into the tumor, go beyond the blood vessels, and travel to nonblooded sites inaccessible in conventional therapies. In addition, the above-mentioned cells are characterized by a high ability to take up the protein "boxes" we use. The protein "box" load is transferred from the immune system cells directly to the cancer cells, which increases the specificity of drug delivery. This means that the developed system can significantly reduce the toxicity of modern therapies or allow the delivery of a much larger amount of the drug to the tumor, increasing the effectiveness of the treatment. The project aims to investigate at the cellular level the mechanism of the transmission of protein 'boxes' from cells of the immune system to cancer cells. This will allow not only to identify new interactions between cells, but also to increase the effectiveness of drug delivery to cancer cells. In addition, the project aims to optimize the method of differentiation of transporters to improve their ability to reach the tumor. A series of studies will be carried out to check the safety of this method in preclinical studies in animal models. If the results of this project are positive, a new, targeted drug delivery system to cancer cells will be created. This system will guarantee an increase in the effectiveness of therapy and a reduction in side effects, which may significantly extend the survival period and improve the quality of life of cancer patients, which will be a long-awaited breakthrough in cancer therapy. Project implemented by the Consortium: Medical University of Warsaw together with Cellis sp.z o.o.

With regard to the most important publications, research achievements carried out with the team of prof. Dr hab. Mariusz Ratajczak shed new light on the phenomenon of mobilization, implantation and retention of hematopoietic stem cells (KMM). The results obtained in the study indicate a significant role of the lectin activation pathway of the complement cascade in relation to the phenomenon of pharmacological mobilization, suggesting the potential use of mannose-binding lectin determination in determining the mobilization capacity of the organism. The conducted studies have also shown the inhibitory effect of heme oxygenase (HO-1) on the chemotactic activity of KKM, while enhancing their adhesive properties, making the HO-1 inhibitor a potential tool to improve the treatment of diseases using KKM transplants in patients. Moreover, the role of TLR signaling together with the MyD88 protein (myeloid differentiation primary response) has been shown to enhance HO-1 expression in these cells, which negatively affects the process of their exit from the marrow niche to peripheral blood. For the first time, our research has also shown the participation of the Apolytic enzyme, ie phospholipase C (PLC-B2), in the pharmacologically induced KKM mobilization, in addition to proteolytic enzymes. In addition, the results published in the study demonstrate the role of sphingosine-1 phosphate (S1P) in the bone marrow microenvironment, confirming the concept of the presence of other SDF-1-CXCR4 axes that are involved in implantation, colonization of the marrow niche and retention of hematopoietic stem cells. The results obtained with my participation may contribute to the effective therapy of hematological diseases, the treatment of which is hematopoietic stem cell transplantation.