Publications by authors named "A K Vorobyeva"
Article Synopsis
- Clinical trials for drugs targeting HER3 have struggled due to inefficacy, despite some cancer patients having higher levels of HER3 expression.
- Novel drug delivery methods, such as affibody-based conjugates targeting HER3, are being explored to improve treatment outcomes.
- The study demonstrated that a specific drug conjugate (Z-ABD-Z-mcDM1) showed promising tumor growth inhibition and extended survival in mice with pancreatic cancer compared to other treatments.*
A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using Tc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection.
View Article and Find Full Text PDFPurpose: Fusion of Affibody molecules with an albumin-binding domain (ABD) provides targeting agents, which are suitable for radionuclide therapy. To facilitate clinical translation, the low immunogenic potential of such constructs with targeting properties conserved is required.
Methods: The HER2-targeting Affibody molecule ZHER2:2891 was fused with a deimmunized ABD variant and DOTA was conjugated to a unique C-terminal cysteine.
Affibody-mediated PNA-based pretargeting shows promise for HER2-expressing tumor radiotherapy. In our recent study, a 15-mer Z-HP15 affibody-PNA conjugate, in combination with a shorter 9-mer [Lu]Lu-HP16 effector probe, emerged as the most effective pretargeting strategy. It offered a superior tumor-to-kidney uptake ratio and more efficient tumor targeting compared to longer radiolabeled effector probes containing 12 or 15 complementary PNA bases.
View Article and Find Full Text PDFArticle Synopsis
- Developing protein therapeutics requires optimizing their pharmacokinetic and pharmacodynamic properties, particularly to prolong their half-lives in the body.
- A study compared various half-life extension technologies (PAS polypeptides, XTEN polypeptides, and an albumin binding domain) using an HER2 affibody-drug conjugate, revealing that while these extensions lowered HER2 affinity slightly, they maintained cytotoxic effectiveness.
- The results indicated that the ABD-enhanced construct had the highest tumor uptake and the best overall performance, despite not having the longest half-life compared to others tested.