Research Department of Translational Oncology

Head of Department— Maxim Shevtsov, PhD in Biology

Tasks

Development and implementation of new diagnostic and treatment methods for malignant central nervous system (CNS) tumors.

Focus areas

Development of RAS70 peptide agent against membrane-bound HSP70 on cancer cells for targeted intraoperative imaging of malignant tumors.

Project description

The molecular chaperone Hsp70, in addition to its intracellular localisation, is expressed on the surface of the plasma membrane of cancer cells, but not on normal body cells, which makes it possible to use this protein as a target for the development of new drugs for the diagnosis and therapy (theranostics) of malignant tumors. Previously, the Institute of Cytology of the Russian Academy of Sciences (St. Petersburg, Russia) showed that tumors of various localisations (including glioblastoma multiforme, colorectal cancer, gastric and oesophageal cancer, breast cancer, non-small cell lung cancer, etc.) express Hsp70 on the membrane, and the degree of protein expression correlates with the metastatic aggressiveness and invasiveness of neoplasms. A number of agents have been developed for the detection of Hsp70-positive cancer cells, including monoclonal antibodies, Fab antibody fragments and specific peptides. In particular, a number of preclinical studies have demonstrated that the RAS70 peptide specifically recognises primary tumors and metastases using magnetic resonance imaging (MRI), positron emission tomography (PET) and epifluorescence microscopy. This study aims to develop a new drug based on the specific RAS70 peptide against the membrane-bound protein Hsp70 on cancer cells for intraoperative diagnostic imaging of tumors and metastases with the possibility of their subsequent radical removal.

Structure

Specialists

Maxim Shevtsov, Head of Department
Natalia Yudintseva, Leading Researcher
Danila Bobkov, Senior Researcher
Alexander Kim, Senior Researcher
Ruslana Tagaeva, Junior Researcher
Anastasia Nechaeva, Junior Researcher
Daria Goncharova, Research Assistant

Newly developed and implemented technologies

A peptide was developed and characterised that specifically recognises cancer cells carrying the heat shock protein Hsp70 on their surface.

Methods were developed to assess the expression of molecular chaperones in malignant tumors of the central nervous system.

Major publications

Shevtsov M., Stangl S., Nikolaev B., Yakovleva L., Marchenko Y., Tagaeva R., Sievert W., Pitkin E., Mazur A., Toltoy P., Galibin O., Ryzhov V., Steiger K., Smirnov O., Khachatryan W., Chester K., Multhoff G. Granzyme B functionalized nanoparticles targeting membrane Hsp70-positive tumors for multimodal cancer theranostics. Small. 2019; 15(13):e1900205. WoS IF = 10.856, Q1
Goryaynov S. A., Okhlopkov V. A., Golbin D. A., Chernyshov K. A., Svistov D. V., Martynov B. V., Kim A. V., Byvaltsev V. A., Pavlova G. V., Batalov A., Konovalov N. A., Zelenkov P. V., Loschenov V. B., Potapov A. A. Fluorescence Diagnosis in Neurooncology: Retrospective Analysis of 653 Cases. Front Oncol. 2019;9:830. WoS IF = 4.848, Q1
Shevtsov M., Sato H., Multhoff G., Shibata A. Novel approaches to improve the efficacy of immuno-radiotherapy. Frontiers in Oncology. 2019;9:156. WoS IF = 4.25, Q1
Shevtsov M., Pitkin E., Ischenko A., Stangl S., Khachatryan W., Galibin O., Edmond S., Lobinger D., Multhoff G. Ex vivo Hsp70-activated NK cells in combination with PD-1 inhibition significantly increase overall survival in preclinical models of glioblastoma and lung cancer. Frontiers in Immunology. 2019;10:454. WoS IF = 4.716, Q1
Stangl S., Tei L., De-Rose F., Reder S., Martinelli J., Sievert W., Shevtsov M., Öllinger R., Rad R., Schwaiger M., Alessandria C.D., Multhoff G. Preclinical evaluation of the Hsp70 peptide tracer TPP-PEG24-DFO[89Zr] for tumor-specific PET/CT imaging. Cancer Research. 2018;78(21):6268-628. WoS IF = 8.378, Q1
Shevtsov M., Nikolaev B., Marchenko Y., Yakovleva L., Skvorzov N., Mazur A., Tolstoy P., Ryzhov V., Multhoff G. Targeting experimental glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs). International Journal of Nanomedicine. 2018;13:1471-1482. WoS IF = 4.471, Q1
Stangl S., Tontcheva N., Sievert W., Shevtsov M., Niu M., Schmid T. E., Pigorsch S., Combs S. E., Haller B., Balermpas P., Rödel F., Rödel C., Fokas E., Krause M., Linge A., Lohhaus F., Baumann M., Tinhofer I., Budach V., Stuschke M., Grosu A.L., Abdollahi A., Debus J., Belka C., Maihöfer C., Mönnich D., Zips D., Multhoff G. Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). International Journal of Cancer. 2018;142(9):1911-1925. WoS IF = 4.982, Q1
Shevtsov M. A., Parr M. A., Ryzhov V. A., Zemtsova E. G., Ponomareva A. N., Smirnov V. M., Multhoff G. Zero-valent Fe confined mesoporous silica nanoparticles (Fe(0)@MCM-41) for targeting experimental orthotopic glioma in rats. Scientific Reports. 2016;6:29247. WoS IF = 4.011, Q1

Patents and inventions

Contacts

Maxim Shevtsov, Head of Department
е-mail: shevtsov-max@mail.ru