Article
Biochemistry & Molecular Biology
Paloma Lozano-Picazo, Cristina Castro-Dominguez, Augusto Luis Bruno, Alejandro Baeza, Adelia S. Martinez, Patricia A. Lopez, Angela Castro, Yassmin Lakhal, Elena Montero, Luis Colchero, Daniel Gonzalez-Nieto, Francisco Javier Rojo, Fivos Panetsos, Milagros Ramos, Rafael Daza, Alfonso M. Ganan-Calvo, Manuel Elices, Gustavo Victor Guinea, Jose Perez-Rigueiro
Summary: High-performance regenerated silk fibers can be efficiently produced through straining flow spinning technique. These fibers not only have enhanced biocompatibility but also can be conveniently functionalized, such as producing fluorescent fibers for tracking, combining fibers with enzymes for catalytic properties, and modifying fibers with cell-adhesion motifs for modulating cell adherence.
Article
Biochemistry & Molecular Biology
Johanna Voigt, Christoph Meyer, Frank Bordusa
Summary: Bispecific antibodies (bsAbs) are emerging as a leading class of immunotherapies for cancer treatment. This study presents novel chemo-enzymatic and purely enzymatic strategies for generating bispecific antibody fragments, which show promising results in breast cancer cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Medicinal
Yeji Hong, Su-Min Nam, Aree Moon
Summary: Engineering approaches using ADCs and bsAbs aim to overcome limitations of conventional chemotherapies and therapeutic antibodies. Cancer immunotherapies have shown clinical success, but overactive immune systems remain a challenge. A multi-target platform strategy is advantageous in the complex tumor environment. Currently, hundreds of ADCs and bsAbs are in clinical development, showing promising therapeutic activity. These strategies selectively deliver drugs to tumor cells and can be used as therapeutic approaches for various cancers.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Christian B. M. Poulie, Emanuel Sporer, Lars Hvass, Jesper T. Jorgensen, Paul J. Kempen, Sara I. Lopes van den Broek, Vladimir Shalgunov, Andreas Kjaer, Andreas Jensen, Matthias M. Herth
Summary: Combining nanotechnology and bioorthogonal chemistry offers the possibility of developing next generation nanomedicines. These nanomedicines can passively target tumors for drug delivery, and bioorthogonal chemistry allows for pretargeting to improve target-specific drug accumulation and induce internalization processes or controlled drug release.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Immunology
Geraldo Balieiro Neto, Jair Rodini Engracia Filho, Fabio Enrique Lemos Budino, Acyr Wanderley de Paula Freitas, Weber Vilas Boas Soares
Summary: The use of antimicrobial growth promoters is banned due to drug residues and increased bacterial resistance. Immunizing chickens with specific antigens to generate antibodies can be an alternative to antibiotics. However, protein impurities and biotin concentrations in IgY antibody samples may affect the accuracy of diagnostic tests.
Article
Chemistry, Medicinal
Christoph Bredack, Martin R. Edelmann, Edilio Borroni, Luca C. Gobbi, Michael Honer
Summary: Bioorthogonal pretargeted imaging using antibody-based click chemistry is a viable approach for molecular imaging. The study successfully demonstrated the labeling of A beta plaques in vitro, ex vivo, and in vivo using a brain-penetrating antibody. Further experiments are needed to optimize the stability and reactivity of the reactants.
Article
Chemistry, Multidisciplinary
Fabien Thoreau, Peter A. Szijj, Michelle K. Greene, Lea N. C. Rochet, Ioanna A. Thanasi, Jaine K. Blayney, Antoine Maruani, James R. Baker, Christopher J. Scott, Vijay Chudasama
Summary: In recent years, there has been growing interest in protein-protein conjugation, especially in the context of bispecific antibodies (bsAbs) and their therapeutic applications. These molecules contain two paratopes capable of binding two distinct epitopes, enabling complex biological functions that monospecific antibodies cannot achieve. While traditional methods for bsAb construction involve protein engineering, recent developments have led to the emergence of chemical methods that offer increased modularity, speed, and the potential for further functionalization. However, most of these approaches lack the inclusion of a fragment crystallizable (Fc) modality, which provides effector function and increased half-life. In this study, a novel method using disulfide rebridging and click-chemistry has been reported for the generation of Fc-containing, IgG-like mono- and bispecific antibodies, referred to as synthetic antibodies (SynAbs). A T cell engager SynAb, FcCD20-(FabHER2)-FabCD3, has been successfully constructed and demonstrated the expected biological functions, including the ability to effectively kill HER2+ target cells in co-culture assays with T cells.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Bianca N. Lourenco, Ruben F. Pereira, Cristina C. Barrias, Claudia Fischbach, Carla Oliveira, Pedro L. Granja
Summary: The study suggests CD44v6 as a marker for early detection of gastric cancer and introduces a nanoscale system that selectively targets CD44v6-expressing GC cells. The results confirm the specific targeting ability of the system, highlighting its potential for early diagnosis and therapy of GC.
Review
Oncology
Tiancheng Zhang, Youpei Lin, Qiang Gao
Summary: Advances in antibody engineering have led to the development of innovative antibody drugs called bispecific antibodies (bsAbs). These bsAbs have attracted significant interest in cancer immunotherapy by targeting two different antigens and enhancing tumor killing. Cadonilimab (PD-1 x CTLA-4) is the first approved bsAb targeting dual inhibitory checkpoints, confirming the feasibility of bsAbs in immunotherapy. This review analyzes the mechanisms and emerging applications of bsAbs targeting immunomodulatory checkpoints in cancer immunotherapy.
CANCER BIOLOGY & MEDICINE
(2023)
Article
Nanoscience & Nanotechnology
Ruili Wei, Yansong Dong, Yalan Tu, Shiwei Luo, Xinrui Pang, Wanli Zhang, Wang Yao, Wenjie Tang, Huikang Yang, Xinhua Wei, Xinqing Jiang, Youyong Yuan, Ruimeng Yang
Summary: The development of novel activatable photosensitizers with plasma membrane targeting ability is crucial for smart photodynamic therapy (PDT). This study combines a tumor acidity-activatable photosensitizer with a two-step bioorthogonal pretargeting strategy, effectively anchoring photosensitizers to the plasma membrane for enhanced therapeutic efficacy in anticancer therapy. The activation and click reaction-based localization of photosensitizers on tumor cells surface result in cytotoxic reactive oxygen species-induced cell membrane damage and apoptosis upon laser irradiation.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemical Research Methods
Maciej Kujawski, Lin Li, Harry Li, Paul J. Yazaki, Piotr Swiderski, John E. Shively
Summary: The study demonstrates the generation of potent cytotoxic dbBiTERs on T-cell surfaces, offering a novel approach for antigen-specific T-cell therapy.
BIOTECHNOLOGY JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Karine Porte, Maxime Riberaud, Remi Chatre, Davide Audisio, Sebastien Papot, Frederic Taran
Summary: The advent of bioorthogonal chemistry has enabled ambitious applications of unnatural chemical reactions within living organisms, a long-sought goal in chemical biology. This review highlights the progress in understanding fundamental biological processes and the development of novel imaging and therapeutic strategies using bioorthogonal chemistry in animal models.
Article
Medical Laboratory Technology
Ummuhan Oncul, Fatma Tuba Eminoglu, Engin Kose, Ozlem Dogan, Elif Ozsu, Zehra Aycan
Summary: The study found that high biotin concentrations in Roche assays can affect the results of PTH, 25-OHD, and TSH, leading to a risk of misdiagnosis. However, SMP neutralization can efficiently suppress this interference.
CLINICAL BIOCHEMISTRY
(2022)
Article
Oncology
Odd L. Gammelgaard, Mikkel G. Terp, Christian Renn, Aran F. Labrijn, Oliver Hamaker, Aaraby Y. Nielsen, Henriette Vever, Soren Wk Hansen, Morten F. Gjerstorff, Christa E. Muller, Paul Whi Parren, Henrik J. Ditzel
Summary: The study demonstrates that combining different anticancer activities of anti-CD73 antibodies into a biparatopic bispecific antibody enhances enzyme inhibitory activity, alleviates T-cell suppression, and prolongs the survival of tumor-bearing mice. The bispecific antibody facilitates more efficient internalization of cell surface CD73 and stimulates Fc-mediated engagement of human immune effector cells in vitro and in vivo.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, General & Internal
Dong Liu, Yacob Berhane Gebreab, Jian Hu, Lili Zhou, Ning Zhang, Hui Tong, Bin Chen, Xiaoqin Wang
Summary: This study developed a new biotin interference-resisting method based on a biotin-streptavidin chemiluminescence immunoassay. By testing streptavidin-coated magnetic microparticles (M) of different concentrations in an automated setting, it was found that higher concentrations of M had a stronger ability to resist biotin interference. The developed method (M3) showed improved ability to resist biotin interference, achieved full automation, and met the general laboratory quality requirements.
Article
Pharmacology & Pharmacy
Tianqi Xu, Jie Zhang, Maryam Oroujeni, Maria S. Tretyakova, Vitalina Bodenko, Mikhail Belousov, Anna Orlova, Vladimir Tolmachev, Anzhelika Vorobyeva, Torbjorn Graslund
Summary: This study investigated the influence of linker length and composition on the functionality and biodistribution of targeted drug conjugates, finding that longer linkers decreased affinity to HER2 and serum albumin but reduced liver uptake. This provides important insights into molecular design for developing drug conjugates with reduced hepatic uptake.
Article
Pharmacology & Pharmacy
Vladimir Chernov, Ekaterina Dudnikova, Roman Zelchan, Anna Medvedeva, Anstasiya Rybina, Olga Bragina, Viktor Goldberg, Albina Muravleva, Jens Sorensen, Vladimir Tolmachev
Summary: This study evaluated the safety, biodistribution, and dosimetry of [Tc-99m]Tc-TG in lymphoma patients, and found that it can be considered as an additional diagnostic method for imaging GLUT receptors in these patients.
Article
Pharmacology & Pharmacy
Yongsheng Liu, Anzhelika Vorobyeva, Anna Orlova, Mark W. Konijnenberg, Tianqi Xu, Olga Bragina, Annika Loftenius, Erica Rosander, Fredrik Y. Frejd, Vladimir Tolmachev
Summary: HER2-targeted radionuclide therapy shows effectiveness in treating HER2-expressing malignant tumors without kidney toxicity.
Article
Pharmacology & Pharmacy
Javad Garousi, Tianqi Xu, Yongsheng Liu, Olga Vorontsova, Sophia Hober, Anna Orlova, Vladimir Tolmachev, Torbjorn Graslund, Anzhelika Vorobyeva
Summary: The developed drug conjugate, ADAPT6-ABD-mcDM1, showed significant therapeutic efficacy in mice bearing HER2-expressing ovarian cancer xenografts by delaying tumor growth and increasing median survival without inducing toxicity. The evaluation of imaging probes demonstrated the suitability of small scaffold proteins as diagnostic companions for potential therapy stratification.
Article
Pharmacology & Pharmacy
Yongsheng Liu, Shengze Yu, Tianqi Xu, Vitalina Bodenko, Anna Orlova, Maryam Oroujeni, Sara S. Rinne, Vladimir Tolmachev, Anzhelika Vorobyeva, Torbjorn Graslund
Summary: This study evaluated the use of Ga-68 and In-111-labeled affibody construct NODAGA-(HE)(3)-Z(IGF-1R:4551) for the imaging of IGF-1R expression using PET and SPECT techniques. The results showed that these imaging probes could specifically bind to IGF-1R both in vitro and in vivo, demonstrating their potential for visualizing IGF-1R expression in malignant tumors.
Article
Pharmacology & Pharmacy
Maryam Oroujeni, Ekaterina A. Bezverkhniaia, Tianqi Xu, Yongsheng Liu, Evgenii Plotnikov, Ida Karlberg, Eva Ryer, Anna Orlova, Vladimir Tolmachev, Fredrik Y. Frejd
Summary: Radionuclide molecular imaging can accurately assess the expression of molecular targets in disseminated cancers, enabling stratification of patients for specific therapies. In this study, the targeting properties of an Affibody-based probe, AC12-GGGC, labeled with technetium-99m, were evaluated for imaging B7-H3-expressing tumors. The results showed that [Tc-99m]Tc-AC12-GGGC had high tumor uptake and tumor-to-blood ratio, making it a promising candidate for further development.
Article
Medicine, General & Internal
O. D. Bragina, V. Chernov, S. M. Deyev, V. M. Tolmachev
Summary: This review discusses the diagnostic methods and treatment requirements for HER2-positive breast cancer, and presents the latest trends in radionuclide diagnosis using alternative scaffold proteins and their applications in clinical practice.
BYULLETEN SIBIRSKOY MEDITSINY
(2022)
Article
Biochemistry & Molecular Biology
Tianqi Xu, Alexey Schulga, Elena Konovalova, Sara S. Rinne, Hongchao Zhang, Olga Vorontsova, Anna Orlova, Sergey M. Deyev, Vladimir Tolmachev, Anzhelika Vorobyeva
Summary: Pancreatic cancer (PC) is an aggressive malignancy, and targeted therapies could improve its treatment. Overexpression of HER3 and EpCAM in PC is associated with poor prognosis. The study investigated whether co-targeting HER3 with MM-121 and EpCAM with Ec1-LoPE could enhance therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Fanny Lundmark, Ayman Abouzayed, Sara S. S. Rinne, Vasiliy Timofeev, Nadezhda Sipkina, Maria Naan, Anastasia Kirichenko, Maria Vasyutina, Daria Ryzhkova, Vladimir Tolmachev, Ulrika Rosenstrom, Anna Orlova
Summary: Prostate cancer is the most diagnosed cancer and leading cause of cancer-related deaths in men. This study presents the preclinical characterization and evaluation of a radiotracer that targets both PSMA and GRPR for PET imaging of prostate cancer. The findings support the clinical translation of the radiotracer and represent a step towards its first clinical trial.
Article
Medicine, General & Internal
O. D. Bragina, L. A. Tashireva, V. Chernov, S. M. Deyev, V. M. Tolmachev
Summary: The use of 99mTc-DARPinG3 can serve as an informative prognostic criteria for assessing the HER2/neu status in primary breast cancer, and a mathematical model was developed for prediction.
BYULLETEN SIBIRSKOY MEDITSINY
(2022)
Article
Oncology
Yongsheng Liu, Tianqi Xu, Anzhelika Vorobyeva, Annika Loftenius, Vitalina Bodenko, Anna Orlova, Fredrik Y. Frejd, Vladimir Tolmachev
Summary: Affibody molecules are artificial proteins that can target cancer-related molecular abnormalities. Clinical studies have shown that they can be used for radionuclide diagnostics and therapy. This study demonstrated that re-engineered Affibody molecules can increase the survival of mice with human tumors, and the combination of Affibody molecules and a monoclonal antibody was the most effective treatment.
Article
Oncology
Olga Bragina, Vladimir Chernov, Alexey Schulga, Elena Konovalova, Sophia Hober, Sergey Deyev, Jens Sorensen, Vladimir Tolmachev
Summary: The overexpression of HER2 receptor in certain breast cancers can be successfully treated with trastuzumab and pertuzumab antibodies. Radionuclide imaging can assist in selecting patients for antibody treatment. The small-sized radiolabelled scaffold proteins ADAPT6 and DARPin have shown excellent imaging properties and promising results in the imaging of HER2 in preclinical and Phase I clinical trials.
Article
Medicine, General & Internal
Ayman Abouzayed, Jesper Borin, Fanny Lundmark, Anastasiya Rybina, Sophia Hober, Roman Zelchan, Vladimir Tolmachev, Vladimir Chernov, Anna Orlova
Summary: A kit was successfully prepared for prospective use in an early-phase clinical study, allowing for one-pot single-step radiolabeling with technetium-99m. The radiolabeled peptide maintained its binding properties and showed good safety in animal models after 18 months of storage. Therefore, the prepared kit can be further evaluated for clinical application.
Article
Biochemistry & Molecular Biology
Ayman Abouzayed, Panagiotis Kanellopoulos, Alisa Gorislav, Vladimir Tolmachev, Theodosia Maina, Berthold A. Nock, Anna Orlova
Summary: This study presents a new GRPR antagonist with improved stability and specificity for the theranostics of prostate cancer. In vitro and in vivo experiments showed that the new compound demonstrated higher stability and selective targeting, indicating its potential therapeutic value.
Article
Medicine, General & Internal
O. D. Bragina, S. M. Deyev, E. Yu Garbukov, V. E. Goldberg, V. I. Chernov, V. M. Tolmachev
Summary: This study compared the diagnostic efficacy of two diagnostic agents, [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3, in HER2-positive breast cancer patients. The results showed that [(99)mTc]Tc-ADAPT6 had higher accumulation values, making it a more promising diagnostic agent.
BYULLETEN SIBIRSKOY MEDITSINY
(2023)