Aleksandra Sokolowska-Wedzina
University of Wrocław
CytotoxicityFusion proteinOligopeptideInternalizationFunction (biology)AntigenMolecular biologyCytotoxic T cellAntibodyReceptorChemistryPhage displayConjugateIn vitroMonomethyl auristatin EEndocytosisFibroblast growth factor receptor 1Cancer researchBiochemistryFibroblast growth factorFibroblast growth factor receptorBiologyCell biologyCancer cell
12Publications
7H-index
100Citations
Publications 12
Newest
#1Marta Poźniak (UWr: University of Wrocław)
#2Natalia Porębska (UWr: University of Wrocław)H-Index: 3
Last. Łukasz Opaliński (UWr: University of Wrocław)H-Index: 7
view all 10 authors...
BACKGROUND Antibody drug conjugates (ADCs) represent one of the most promising approaches in the current immuno-oncology research. The precise delivery of cytotoxic drugs to the cancer cells using ADCs specific for tumor-associated antigens enables sparing the healthy cells and thereby reduces unwanted side effects. Overexpression of fibroblast growth factor receptor 1 (FGFR1) has been demonstrated in numerous tumors and thereby constitutes a convenient molecular target for selective cancer trea...
1 CitationsSource
Cancer is currently the second most common cause of death worldwide. The hallmark of cancer cells is the presence of specific marker proteins such as growth factor receptors on their surface. This feature enables development of highly selective therapeutics, the protein bioconjugates, composed of targeting proteins (antibodies or receptor ligands) connected to highly cytotoxic drugs by a specific linker. Due to very high affinity and selectivity of targeting proteins the bioconjugates recognize ...
1 CitationsSource
#1Marta Pozniak (UWr: University of Wrocław)H-Index: 1
#2Aleksandra Sokolowska-Wedzina (UWr: University of Wrocław)H-Index: 7
Last. Lukasz Opalinski (UWr: University of Wrocław)H-Index: 3
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Fibroblast growth factor receptor 1 (FGFR1) transmits signals through the plasma membrane regulating essential cellular processes like division, motility, metabolism and death. Overexpression of FGFR1 is observed in numerous tumors and thus constitutes an attractive molecular target for selective cancer treatment. Targeted anti-cancer therapies aim for the precise delivery of drugs into cancer cells, sparing the healthy ones and thus limiting unwanted side effects. One of the key steps in target...
3 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...
15 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
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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...
10 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...
13 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
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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
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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...
26 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...
12 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...
12 CitationsSource