Marek Kovář

Our group also investigates cancer immunotherapy by complexes of IL-2 and anti-IL-2 mAbs (i.e., IL-2 complexes). These IL-2 complexes have a higher in vivo biological activity than the free IL-2. Moreover, the IL-2 complexes exert selective stimulatory activity either for CD25⁺ cell subsets or for CD122^high cell subsets, whereby this feature is dictated by the clone of anti-IL-2 mAb used. Aside from this, we collaborate with Jamie B. Spangler’s group from the Johns Hopkins University on the development of immunocytokines (ICs), which mimic the abovementioned IL-2 complexes but are in fact fused (chimeric) recombinant proteins. 

Cancer immunotherapy made a vast progress in the past two decades and the introduction of immune checkpoint inhibitors (ICIs) had significantly improved the prognosis of patients with several kinds of cancer. IL-2 complexes and ICs do exhibit anticancer activity and we study their potential to improve cancer immunotherapy by ICIs (mostly anti-CTLA-4 and/or anti-PD-1 mAbs). On top of that, we evaluate the possibility of combining immunotherapy by IL-2 complexes with chemotherapy based on the use of polymer nanotherapeutics. The rationale here is that polymer nanotherapeutics have a lower systemic toxicity and, most importantly, a lower immunosuppressive activity than conventional cytostatic drugs do.

Research objectives

1. The development of new polymer nanotherapeutics based on HPMA copolymers bearing a cytostatic drug (gemcitabine, doxorubicin, mitoxantrone, docetaxel, platinum-based drugs) covalently attached by a defined covalent bond; evaluation of their anticancer activities in vitro and in vivo.
2. Biological activity of IL-2 complexes or analogical chimeric recombinant proteins (immunocytokines) with particular focus on their potential to improve cancer immunotherapy via ICIs.
3. To investigate the therapeutic potential of chemoimmunotherapy based on polymer nanotherapeutics and IL-2 complexes or immunocytokines.