Jacek Otlewski
University of Wrocław
Binding siteBiophysicsMutantMolecular biologyCytotoxic T cellReceptorEnzymeChemistryPhage displayTrypsin inhibitorChymotrypsinTrypsinProtein structureBiochemistryStereochemistryFibroblast growth factorCrystallographyFibroblast growth factor receptorBiologyCell biologyCancer cell
153Publications
44H-index
4,499Citations
Publications 152
Newest
#1Karolina Świderska (UWr: University of Wrocław)H-Index: 2
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
In the rapidly developing field of targeted cancer therapy there is growing interest towards therapeutics combining two or more compounds to achieve synergistic action and minimize the chance of cancer resistance to treatment. We developed a fibroblast growth factor 2 (FGF2)-conjugate bearing two cytotoxic drugs with independent mode of action: α-amanitin and monomethyl auristatin E. Drugs are covalently attached to the targeting protein in a site-specific manner via maleimide-thiol conjugation ...
7 CitationsSource
#1Łukasz Opaliński (UWr: University of Wrocław)H-Index: 7
#2Jakub Szymczyk (UWr: University of Wrocław)H-Index: 2
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 7 authors...
Fibroblast growth factor receptor 1 (FGFR1) is a plasma membrane protein that transmits signals from the extracellular environment, regulating cell homeostasis and function. Dysregulation of FGFR1 leads to the development of human cancers and noncancerous diseases. Numerous tumors overproduce FGFR1, making this receptor a perspective target for cancer therapies. Antibody-drug conjugates (ADCs) are highly potent and selective anticancer agents. ADCs are composed of antibodies (targeting factors) ...
7 CitationsSource
#1Aleksandra Borek (UWr: University of Wrocław)H-Index: 3
#2Aleksandra Sokolowska-Wedzina (UWr: University of Wrocław)H-Index: 7
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 4 authors...
Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage displ...
12 CitationsSource
#1Alicja M. Sochaj-Gregorczyk (UWr: University of Wrocław)H-Index: 3
#2Patryk Ludzia (UWr: University of Wrocław)H-Index: 3
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 6 authors...
In our previous work we demonstrated that a small protein called affibody can be used for a cytotoxic conjugate development. The anti-HER2 affibody was armed with one moiety of a highly potent auristatin E and specifically killed HER2-positive cancer cells with a nanomolar IC50. The aim of this study was to improve the anti-HER2 affibody conjugate by increasing its size and the number of conjugated auristatin molecules. The affibody was fused to the Fc fragment of IgG1 resulting in a dimeric con...
9 CitationsSource
#1Łukasz Opaliński (UWr: University of Wrocław)H-Index: 7
#2Aleksandra Sokolowska-Wedzina (UWr: University of Wrocław)H-Index: 7
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
Fibroblast growth factors (FGFs) and their plasma membrane-localized receptors (FGFRs) play a key role in the regulation of developmental processes and metabolism. Aberrant FGFR signaling is associated with the progression of serious metabolic diseases and human cancer. Binding of FGFs to FGFRs induces receptor dimerization and transphosphorylation of FGFR kinase domains that triggers activation of intracellular signaling pathways. Following activation, FGFRs undergo internalization and subseque...
11 CitationsSource
#1Lukasz Opalinski (UWr: University of Wrocław)H-Index: 3
#2Martyna Szczepara (UWr: University of Wrocław)H-Index: 3
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
Abstract Fibroblast growth factors (FGFs) and their plasma membrane-localized receptors (FGFRs) transduce signals that regulate developmental processes and metabolism. In numerous cancer types genetic aberrations of FGFR1 lead to its uncontrolled activation. To circumvent the unrestrained signal transduction, several intramolecular inhibitory mechanisms within FGFR1 have evolved. In vitro experiments with receptor truncation have demonstrated that the N-terminal D1 domain of FGFR1 negatively reg...
4 CitationsSource
#1Aleksandra Sokolowska-Wedzina (UWr: University of Wrocław)H-Index: 7
#2Grzegorz ChodaczekH-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 6 authors...
Targeted delivery of anti-cancer drugs using antibodies specific for tumor-associated antigens represents one of the most important approaches in current immuno-oncology research. Fibroblast growth factor receptor 1 (FGFR1) has been demonstrated to be a high-frequency targetable oncogene specific for smoking-associated lung cancers, present in over 20% of lung squamous cell carcinoma cases. This report describes the generation of a potent, fully human antibody fragment in scFv-Fc format efficien...
20 CitationsSource
#1Mateusz Adam Krzyscik (UWr: University of Wrocław)H-Index: 4
#2Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 9 authors...
Antibody–drug conjugates (ADCs) are a new class of anticancer therapeutics that combine the selectivity of targeted treatment, ensured by monoclonal antibodies, with the potency of the cytotoxic agent. Here, we applied an analogous approach, but instead of an antibody, we used fibroblast growth factor 2 (FGF2). FGF2 is a natural ligand of fibroblast growth factor receptor 1 (FGFR1), a cell-surface receptor reported to be overexpressed in several types of tumors. We developed and characterized FG...
6 CitationsSource
#1K.W. Swiderska (UWr: University of Wrocław)H-Index: 1
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
Abstract Recent advances in site-specific protein modification include the increasingly popular incorporation of unnatural amino acid(s) using amber codon, a method developed by Schultz and coworkers. In this study, we employ this technique to introduce propargyllysine (PrK) in human fibroblast growth factor 2 (FGF2). Owing to an alkyne moiety in its side chain, PrK is compatible with Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). We successfully tested CuAAC-mediated conjugatio...
7 CitationsSource
#1Michal Lobocki (UWr: University of Wrocław)H-Index: 3
#2Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 6 authors...
Site-specific conjugation is a leading trend in the development of protein conjugates, including antibody–drug conjugates (ADCs), suitable for targeted cancer therapy. Here, we present a very efficient strategy for specific attachment of a cytotoxic drug to fibroblast growth factor 1 (FGF1), a natural ligand of FGF receptors (FGFRs), which are over-expressed in several types of lung, breast, and gastric cancers and are therefore an attractive molecular target. Recently, we showed that FGF1 fused...
9 CitationsSource