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Project

Identification and analysis of early prognostic markers of bladder cancer using generated nanobodies

Funder: Russian Science Foundation

Funding period
0
Funding amount
Abstract
The project is aimed at solving a highly relevant medical problem - finding the most informative early prognostic biomarkers for bladder cancer and developing a non-invasive, technically simple, cost-effective diagnostic method for quantitative analysis of these markers in the patient's urine, which, with high reliability, reproducibility, sensitivity and specificity, identify patients with bladder cancer, preferably at the earliest stages of development of this dangerous and frequently encountered disease, which is extremely inconvenient in terms of diagnosis and monitoring. We plan to use for research of early prognostic markers of bladder cancer the technology of generating monoclonal recombinant single-domain antibodies ( “nanobodies”), which is new for research in this area, but already proven (including in the work of our team) as very effective for solving various scientific problems of biology and medicine. We plan to focus primarily on the study of biomarkers of extracellular vesicles (exosomes) of urine. The contents of the vesicles are stable in the urine and are protected from exogenous RNases and proteases, thanks to the protective membrane, as well as binding to RNA-binding or DNA-binding proteins or lipoprotein complexes. Unlike other urine components, vesicles remain stable during long-term storage and multiple freeze-thaw cycles, making them an attractive source for biomarker research. Several studies have shown that cancer cells release more extracellular vesicles than normal cells, and that the biomolecular content of the vesicles reflects the characteristics of these components in the cell of origin. The main goals of the project are as follows.
1) Generation of a set of new single-domain antibodies (nanobodies) against surface antigens of various types of extracellular vesicles from human urine (cancer patients at different stages of the disease and postoperative observation); these nanobodies will be used to identify, develop new effective methods for isolation and study of different variants of vesicles.
2) Obtaining new tools on the basis of generated nanobodies for the study of promising early prognostic biomarkers (proteins, RNA, metabolites) of bladder cancer.
3) Using previously obtained nanobodies to various human immunoglobulins, we will attempt to isolate and study potential immune complexes existing in the urine (normal and in case of RMP) and try to identify and study antigens in these complexes for their potential to be biomarkers of RMP.
4) We plan to create a bank of urine samples of patients at risk, patients of different stages and forms of bladder cancer (depending on availability and availability), as well as control samples of healthy donors.
5) Based on the analysis and accounting of literature data on promising biomarkers of various types, as well as on the basis of our own developments of new nanobodies to promising protein biomarkers, an attempt will be made to create a prototype of a new non-invasive, technically simple, economical, highly sensitive and specific diagnostic method for quantitative analysis of these markers in the urine of the patient.
We have not yet found references to obtaining nanobodies for the diagnosis of bladder cancer in published scientific articles, so we expect to have some starting advantage in this direction of research.
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Cancer

  • RCDC

    Urologic Diseases

  • HRCS HC

    Generic Health Relevance

  • HRCS HC

    Cancer

  • HRCS RAC

    4.1 Discovery and preclinical testing of markers and technologies

  • Health Research Areas

    Biomedical