Anzhelika Vorobyeva
Uppsala University
CancerBiophysicsMolecular imagingChemistryConjugateIn vitroIn vivoDARPinBiodistributionPretargetingTrastuzumabDOTAAffibody moleculeRadionuclide therapyHer2 expressionCancer researchScaffold proteinBiochemistryMedicinePharmacology
Publications 61
Radiolabeled Affibody-based targeting agent 177Lu-ABY-027, a fusion of an anti-HER2 Affibody molecule with albumin binding domain (ABD) site-specifically labeled at the C-terminus, has demonstrated a promising biodistribution profile in mice; binding of the construct to albumin prevents glomerular filtration and significantly reduces renal uptake. In this study, we tested the hypothesis that site-specific positioning of the chelator at helix 1 of ABD, at a maximum distance from the albumin bindi...
#1O. D. Bragina (RAS: Russian Academy of Sciences)H-Index: 1
#2V. I. Chernov (RAS: Russian Academy of Sciences)H-Index: 3
Last. V. M. Tolmachev (Tomsk Polytechnic University)H-Index: 1
view all 7 authors...
#1Olga Bragina (RAS: Russian Academy of Sciences)H-Index: 4
#2Emma von Witting (KTH: Royal Institute of Technology)H-Index: 4
Last. Vladimir Tolmachev (Uppsala University)H-Index: 61
view all 16 authors...
Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6. METHODS: Twenty-nine patients with prim...
7 CitationsSource
#1Haozhong DingH-Index: 3
#2Tianqi XuH-Index: 2
Last. Anzhelika VorobyevaH-Index: 11
view all 8 authors...
Affibody molecules hold great promise as carriers of cytotoxic drugs for cancer therapy due to their typically high affinity, easy production, and inherent control of the drug molecules' loading and spatial arrangement. Here, the impact of increasing the drug load from one to three on the properties of an affibody drug conjugate targeting the human epidermal growth factor receptor 2 (HER2) was investigated. The affibody carrier was recombinantly expressed as a fusion to an albumin-binding domain...
#1Maryam Oroujeni (Uppsala University)H-Index: 7
#2Sara S. Rinne (Uppsala University)H-Index: 8
Last. Vladimir TolmachevH-Index: 61
view all 10 authors...
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a secon...
#1Hanna TanoH-Index: 1
#2Maryam OroujeniH-Index: 7
Last. Vladimir TolmachevH-Index: 61
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Affibody-mediated PNA-based pretargeting is a promising approach to radionuclide therapy of HER2-expressing tumors. In this study, we test the hypothesis that shortening the PNA pretargeting probes would increase the tumor-to-kidney dose ratio. The primary probe ZHER2:342-SR-HP15 and the complementary secondary probes HP16, HP17, and HP18, containing 9, 12, and 15 nucleobases, respectively, and carrying a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator were designed, syn...
#1Javad Garousi (Uppsala University)H-Index: 13
#2Emma von Witting (KTH: Royal Institute of Technology)H-Index: 4
Last. Sophia Hober (KTH: Royal Institute of Technology)H-Index: 41
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Abstract Molecular recognition in targeted therapeutics is typically based on immunoglobulins. Development of engineered scaffold proteins (ESPs) has provided additional opportunities for the development of targeted therapies. ESPs offer inexpensive production in prokaryotic hosts, high stability and convenient approaches to modify their biodistribution. In this study, we demonstrated successful modification of the biodistribution of an ESP known as ADAPT (Albumin-binding domain Derived Affinity...
1 CitationsSource
#1Tianqi XuH-Index: 2
#2Haozhong DingH-Index: 3
Last. Torbjörn GräslundH-Index: 21
view all 7 authors...
The human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in a variety of cancers and therapies targeting HER2 are routinely used in the clinic. Recently, small engineered scaffold proteins, such as affibody molecules, have shown promise as carriers of cytotoxic drugs, and these drug conjugates may become complements or alternatives to the current HER2-targeting therapies. Here, we investigated if a monovalent HER2-binding affibody molecule, ZHER2:2891, fused with a plasma ...
1 CitationsSource
#1Anders Myrhammar (KTH: Royal Institute of Technology)H-Index: 1
#2Anzhelika Vorobyeva (Uppsala University)H-Index: 11
Last. M. Altai (Lund University)H-Index: 2
view all 9 authors...
Radionuclide molecular imaging of cancer-specific targets is a promising method to identify patients for targeted antibody therapy. Radiolabeled full-length antibodies however suffer from slow clearance, resulting in high background radiation. To overcome this problem, a pretargeting system based on complementary peptide nucleic acid (PNA) probes has been investigated. The pretargeting relies on sequential injections of primary, PNA-tagged antibody and secondary, radiolabeled PNA probe, which ar...