Current projects
“Achieving the Golden Grail in solid tumor treatment”
Grant ERC Proof of Concept, 101113272
Head: Magdalena Król
Macrophage therapy is promising for solid tumor treatment as these cells are continuously recruited into the tumor mass, even the most hypoxic regions. Our pioneering research demonstrated that macrophages are able to take up ferritins loaded with anti-cancer drugs, creating Macrophage-Drug Conjugates (MDCs), and transfer these to cancer cells and kill them, a phenomenon we named TRAIN. In my ongoing ERC Starting Grant PROJECT ‘McHAP’, we have proven that MDCs can be sucessfully used not only to treat solid tumors but also to induce subsequent resistance to the tumor re-challenge. Acquisition of resistance to tumor development after specific therapy is a ‘Golden Grail’ in oncology. Now we aim to turn the MDC technology into a commercial and social value proposition by confirming mechanisms of tumorresistance in tumor-bearing mice and identify immune response. This is crucial to raise interest of and establish a co-development (or licensing) deal with big pharma’s to realize commercialization and clinical uptake of our IP-protected MDC technology. During the ERC PoC project, we will perform high-dimensional spectral flow cytometry, spatial transcriptomics and single-cell transcriptomics of the tumor before and after MDC treatment to identify mechanisms of tumor-resistance and optimize our business case. This project will thus provide proof of concept for the immune activation after the MDC treatment and thus establish the viability, feasibility, commercialization and overall direction for our innovative MDC technology. This project will substantially contribute to bring our MDC technology to the market and clinical practice.
“The role of ferroptotic tumor cells in tumor development by modifying the tumor microenvironment”
GRANT NCN SONATA, Grant No.: 2019/35/D/NZ5/03058
Head: Paulina Kucharzewska-Siembieda
Cancer is one of the leading causes of death in developed countries. For a long time, tumors were thought to be made up of only cancer cells, but research has shown that they live surrounded by other cells, such as fibroblasts, cells of the immune system and endothelial cells of blood vessels, which together form the tumor microenvironment. Cancer cells reprogram the microenvironment cells to promote tumor growth and invasion. Therefore, understanding the interaction between the microenvironment and cancer cells is crucial for the development of new treatments. Hypoxia and nutrient depletion, which are inherent stress factors of the tumor microenvironment, are the result of insufficient blood supply in a rapidly growing tumor, as well as the effect of anti-cancer therapies. Cancer cells respond to the cytotoxic effects of these stress factors either by activating the adaptive processes that enable them to survive, or on the contrary, by cell death. Cell death mainly occurs by necrosis as apoptosis is limited in tumor cells. In contrast to apoptotic cell death, which suppresses tumor development, necrosis may paradoxically promote tumor growth and progression. Therefore, the appearance of a necrotic core in many types of tumors is associated with a poor prognosis in patients. For many years, necrosis was considered an accidental and genetically unprogrammed form of cell death. However, it is now known that there are many types of cell death distinct from apoptosis, which are controlled by specific genetic mechanisms and which morphologically resemble necrosis, such as oncosis, necroptosis and ferroptosis. In my research, I plan to focus on ferroptosis and its role in cancer development. Ferroptosis is cell death caused by excessive oxidation of cell membrane lipids in an iron-dependent process due to oxidative stress. The role of ferroptosis in tumor development remains unclear. Based on previous research, ferroptosis contributes to the inhibition of tumor growth, and interestingly, invasive cancer cells, cancer stem cells and chemotherapy-resistant cancer cells are particularly susceptible to ferroptosis. Thus, the induction of ferroptosis in cancerous tumors seems to be an interesting strategy for anticancer therapies. On the other hand, cancer cells that die as a result of ferroptosis secrete numerous molecules into the extracellular space that may potentially have a tumor-promoting effect by modulating the immune system cells, inducing angiogenesis, and activating tumor cells. Therefore, we suspect that ferroptosis induced, e.g. as a result of anti-cancer therapies, may potentially support the development of cancer and contribute to cancer recurrence by modifying the tumor microenvironment. Furthermore, we believe that tumor hypoxia may play an important role in this phenomenon as it induces the expression of some secreted molecules. Therefore, we believe that it is necessary to study the effect of ferroptotic tumor cells on the tumor microenvironment and to identify the molecular mechanisms of these interactions. In our project, we will perform a series of experiments and analyzes that will verify our hypothesis. These will be experiments conducted using both in vitro cell cultures and animal models. We are convinced that the new knowledge gained during the implementation of this project will not only contribute to a deeper understanding of the biology of cancer, but also in the future may lead to the development of more effective anti-cancer therapies.
Cooperation with Cellis and Innotech4Life
Exploring the potential of Macrophage-Drug Conjugates (MDCs) in cancer therapy through investigating B-cathepsin, developing bioassays, validating protocols, toxins, linkers, and exploring new indications and combination approaches with immunomodulators.
2022-2027
Find more info here.
Past projects
“Entrapment of hypoxic cancer by macrophages loaded with HAP”
2017-2022, Starting Grant, European Research Council, 715048, McHAP
Riding a ‘Trojan horse’ against cancer
2021-2022, European Research Council, 956900; Project Information
”Identification of prognostic and drug-sensitivity biomarkers
in triple-negative breast cancer and results validation in vitro and in vivo”
2018-2022, Polish-Turkish, POLTUR2/PC-TNBC/30/2016 and POLTUR2/6/2018, PC-TNBC
”Entrapment of hypoxic tumor by macrophages loaded with HAP”
2017-2021, Premia on Horizon: MNiSW, 355135/PnH/2017
”Identification of molecular mechanisms of new, cell-based, targeted drug delivery system to solid tumors”
2016-2019, SONATA BIS, No. UMO-2015/18/E/NZ6/00642
“Identification of the type of communications between tumor-associated macrophages and canine mammary cancer cells”
2015-2018, PRELUDIUM, No. UMO-2014/15/N/NZ5/03649
”Inhibition of “side effects” of tumor-associated macrophages in canine mammary cancer”
2014-2017, SONATA, No. UMO-2013/09/D/NZ5/02496
”miRNA expression profiling of canine mammary cancer as a new tool in veterinary oncology”
2012-2015, OPUS, No. 2011/03/B/NZ5/05299
“Evaluation of the usefulness of iron transporters and cells of the immune system as new carriers of substances to the tumor”
2016-2019, Project in cooperation with industry
Head: Bartłomiej Taciak
”Influence of tumor-associated macrophages on canine mammary cancer stem cells”
2015-2017, Iuventus Plus, MNiSW, IP2014021073
”Identification of a role of myeloid-derived suppressor cells in cancer metastasis and immune-suppression in tumor-bearing dogs”
2012-2014, Iuventus Plus, MNiSW, IP2011027171
”Molecular interactions between macrophages and canine mammary cancer cells”
2010-2013, Grant No.: N308012939 MNiSW
”Expression and susbtrates for the ATP-Binding Cassette, responsible for drug-resistance of canine mammary cancer”
2011-2014, Grant No.: N308574990 MNiSW
“Transcriptomic profiles of canine mammary cancer cell lines of various proliferative and anti-apoptotic potential”
2009-2012, Grant No.: N308230536 MNiSW
“Transcriptomic profile of canine mammary tumors of various type and grade”
2006-2009, Grant No.: N30800632/0667 MNiSW