We use cookies.
By using the site, you agree to our Privacy Policy.

Laboratory of the Oncology Research Center of the School of Chemical and Biomedical Technologies

Contract number
075-15-2019-1925
Time span of the project
2019-2021

As of 15.02.2021

26
Number of staff members
36
scientific publications
2
Objects of intellectual property
General information
Name of the project: Development of targeted molecules based on framework proteins for diagnostics and treatment of malignant tumors: theranostic approach

Strategy for Scientific and Technological Development Priority Level: в

Goals and objectives
Project objective: сreation of a laboratory for development of targeted molecules based on framework proteins, specific to molecular targets expressed on tumor cells. The Laboratory will work as a competence center in the domain of development of radiopharmaceuticals for diagnostics and treatment of oncological diseases using methods of nuclear medicine

The practical value of the study

The project is aimed at diagnostic radiopharmaceuticals for the patient selection for targeted therapy, as well as the creation of a new class of drugs for targeted therapy of malignant neoplasms, which will make cancer treatment more personalized and, therefore, more effective. The scientific novelty of the project involves in the use of the DARPin (Design Ankyrin Repeat Protein) scaffold protein in the composition of therapeutic radiopharmaceuticals as a target compound, which allows for a higher contrast in molecular imaging of neoplasms and improved therapeutic properties in comparison with antibody-based radiopharmaceuticals.

As part of the research, new methods for the production and quality control of DARPin G3 and Ec1 variants, specific for HER2 and EpCAM tumor markers, respectively, intended for radionuclide imaging, have been developed. The indicated variants of DARPin G3 and Ec1 were developed in the bacterial system. For the DARPin G3 and Ec1 variants, radionuclide treatments for SPECT have been developed and optimized. Preclinical studies of the obtained radioactively labeled variants of DARPin G3 and Ec1 were carried out, including the results of determining the specificity, internalization after binding by tumor cells, affinity, as well as the assessment of biodistribution and preclinical imaging in animal models of ovarian, pancreatic, kidney and breast cancer; data on cumulativeness, general and chronic toxicity were obtained. Methods for the production and quality control of the DARPin-toxin conjugate intended for targeted therapy have been developed; the toxin is accumulated in the bacterial system; the results of its specificity, affinity, internalization into tumor cells were obtained in vitro, and its inhibitory ability was determined. In vivo tests are in progress.

Clinical trials (phase 1) of two drugs were performed to visualize HER2 expression in breast cancer.

Implemented results of research:

Successful clinical trials (phase 1) of two drugs for imaging HER2 expression in breast cancer have been carried out.

Education and career development:

Within the framework of the project, two courses were delivered. The first course was organized as a series of open online lectures by Uppsala University employees on the topic "Development of protein-based radiopharmaceuticals for biomedical applications" for students in the areas 18.04.01 Chemical technology, 18.06.01 Chemical technology, 12.06.01 Photonics, instrumentation, optical and biotechnical systems and technologies, 20.03.01 Technosphere safety, 20.04.01 Technosphere safety and RSCBT employees.

Within the framework of the second lecture-practical course, the listeners got acquainted with world practices in the field of working with radiopharmaceuticals. The practical course consisted of an introductory lecture and 8 practical sessions. Based on the results of practical exercises, students will gain knowledge in the areas of "protein labeling and preclinical characteristics", "laboratory analyzes of HPLC and ITLC", "tests for in vitro specificity (uptake, retention, internalization)", "saturation, IC50, proliferation", " biodistribution, in vivo specificity, experiments with double isotopes, autoradiography ”.

Organizational and structural changes:

On the basis of the Oncoteranostika Research Center, competencies in the field of technology for creating radiopharmaceuticals are concentrated. The infrastructure for conducting research in vivo and in vitro, including on cell and animal models, has been created and is expanding.

Collaborations:

Research collaborations, publications, scientific events (Swedish-Russian online forum of young scientists) and internships are carried out with the Tomsk Polytechnic University (Russia), Tomsk National Research Medical Center of the Russian Academy of Sciences (Russia), Shemyakin-Ovchinnikov Institute of Bioorganic chemistry (Russia), Uppsala University (Sweden), KTH Royal Institute of Technology (Sweden) and Lund University (Sweden).


Hide Show full
Oroujeni, M., Rinne, S.S., Vorobyeva, A., Loftenius, A., Feldwisch, J., Jonasson, P., Chernov, V., Orlova, A., Frejd, F.Y., Tolmachev, V.
Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake //International Journal of Molecular Sciences. – 2021. – Vol. 22. – No. 2770. DOI:10.3390/ijms22052770 https://www.mdpi.com/1422-0067/22/5/2770
Garousi, J., von Witting, E., Borin, J., Vorobyeva, A., Altai, M., Vorontsova, O., Konijnenberg, M.W., Oroujeni, M., Orlova, A., Tolmachev, V. Hober, S.
Radionuclide therapy using ABD-fused ADAPT scaffold protein: Proof of Principle //Biomaterials. – 2021. – Vol. 266. – P. 120381.
Tolmachev, V., Orlova, A., & Sörensen, J.
The emerging role of radionuclide molecular imaging of HER2 expression in breast cancer //Seminars in Cancer Biology. – Academic Press, 2021. DOI: 10.1016/j.semcancer.2020.10.005 https://www.sciencedirect.com/science/article/pii/S1044579X20302108
Bragina O, von Witting E, Garousi J, Zelchan R, Sandström M, Orlova A, Medvedeva A, Doroshenko A, Vorobyeva A, Lindbo S, Borin J, Tarabanovskaya N, Sörensen J, Hober S, Chernov V, Tolmachev V.
Phase I Study of 99mTc-ADAPT6, a Scaffold Protein-Based Probe for Visualization of HER2 Expression in Breast Cancer. J Nucl Med. 2021 Apr;62(4):493-499. doi: 10.2967/jnumed.120.248799.
Deyev, S.M., Vorobyeva, A., Schulga, A., Abouzayed, A., Gunther, T., Garousi, J., Konovalova, E., Ding, H., Graslund, T., Orlova, A., Tolmachev, V.
Effect of a radiolabel biochemical nature on tumor-targeting properties of EpCAM-binding engineered scaffold protein DARPin Ec1 //International Journal of Biological Macromolecules. – 2020. – Vol. 145. – P. 216-225. DOI: 10.1016/j.ijbiomac.2019.12.147
Tolmachev, V., Orlova, A.
Affibody molecules as targeting vectors for PET imaging //Cancers. – 2020. – Vol. 12. – No. 3. – P. 651. DOI: 10.3390/cancers12030651 https://www.mdpi.com/2072-6694/12/3/651
Vorobyeva A, Konovalova E, Xu T, Schulga A, Altai M, Garousi J, Rinne SS, Orlova A, Tolmachev V, Deyev S.
Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1 // International Journal of Molecular Sciences. – 2020. – Т. 21. – №. 9. – С. 3310, doi: 10.3390/ijms21093310
Tano, H., Oroujeni, M., Vorobyeva, A., Westerlund, K., Liu, Y., Xu, T., Vasconcelos, D., Orlova, A., Karlström, A.E., Tolmachev, V.
Comparative Evaluation of Novel 177Lu-Labeled PNA Probes for Affibody-Mediated PNA-Based Pretargeting //Cancers. – 2021. – Vol. 13. – No. 3. – P. 500. DOI: 10.3390/cancers13030500 https://www.mdpi.com/2072-6694/13/3/500
Other laboratories and scientists
Hosting organization
Field of studies
City
Invited researcher
Time span of the project
Research Centre for Magnetic Resonance in Medicine

ITMO University

Health studies

St. Petersburg

Bendahan David

France

2021-2023

«Smart Sleep» Laboratory

Saratov State University

Health studies

Saratov

Thomas Penzel

2019-2021

Laboratory of Experimental Oncology

N. I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation

Health studies

Moscow

Marcus Conrad

2019-2021