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Jindrich Kopecek

Current Research

Research in the Biomedical Polymers Laboratory focuses on two main areas:

Macromolecular therapeutics – combination chemo- and immunotherapy. Recent research focuses on the design of backbone degradable, long-circulating polymer carriers that contain enzymatically degradable oligopeptide sequences in the main chain. These N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug (epirubicin, gemcitabine, paclitaxel) conjugates have demonstrated initiation of immunogenic cell death, thus activating tumors for subsequent treatment with programmed death pathway (PD-1/PD-L1) blockade. Novel anti-PD-L1 antagonists are being studied. The concept was validated on several animal tumor models.

Drug-free macromolecular therapeutics. A new therapeutic approach for the treatment of B cell malignancies has been developed. The effectiveness of the new system is based on biorecognition events without the participation of low molecular weight drugs. Apoptosis of cells can be initiated by the biorecognition of complementary peptide/oligonucleotide motifs at the cell surface resulting in the crosslinking of slowly internalizing receptors. Drug-free macromolecular therapeutics (DFMT) are composed from two nanoconjugates: 1) bispecific engager, Fab’-MOTIF1 (anti-CD20 Fab’ fragment conjugated with coiled-coil forming peptide or morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MOTIF2)X (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer or human serum albumin grafted with multiple copies of complementary oligopeptide or morpholino oligonucleotide). The efficacy of the system was validated in vitro, in vivo and on cells isolated from patients with various subtypes of B cell malignancies.