Most of the current research of Dr Winiarska is aimed at elucidating the molecular mechanisms of antitumor effects of anti-CD20 monoclonal antibodies (mAbs). CD20, a protein widely expressed on the surface of normal and malignant B-cells, is an excellent molecular target for mAbs. Anti-CD20 mAbs have greatly improved the outcome of patients with B-cell malignancies, such as non- Hodgkin’s lymphomas (NHL) and chronic lymphocytic leukemia (CLL). However, it has been observed that even when patients achieve complete response they eventually relapse and succumb to the neoplastic disease. As of yet, little is known about the molecular mechanisms governing the resistance to anti-CD20 mAbs.
Antitumor action of these antibodies results from triggering effector mechanisms of immune response, namely complementdependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and immunophagocytosis. It has been demonstrated that antitumor effects of anti-CD20 mAbs is strictly correlated with the level of CD20 protein in the cell membrane of tumor cells.
The aim of the research is to identify new key modulators responsible for resistance to anti-CD20 monoclonal antibodybased therapeutic modalities. The team is focused on pathways regulating the expression of CD20 antigen in tumor cells. Dr Winiarska team experiments are performed in models of both the established cancer cell lines and patient-obtained samples. The results of the studies will help to determine potential targets affecting both CDC and ADCC.
This knowledge will be necessary to optimize current therapies for more effective tumor cell destruction by anti-CD20 mAbs in patients with NHL and CLL.