Projects / Programmes
Development of reagents for liquid biopsy-based diagnostic stratification and targeted treatment of breast tumors
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.04 |
Medical and Health Sciences |
Medical biotechnology |
nanobodies, tumor biomarkers, liquid biopsy, diagnostic reagents, in vitro antibody selection
Researchers (6)
Organisations (2)
Abstract
The capacity to identify biologically distinct tumor sub-types according to the expression of specific biomarkers has critically improved the therapy efficiency and minimized the toxicity caused by applying ineffective therapies. It is expected that the progressive integration of the present knowledge with further biomarkers will increase the chance to design optimal targeted therapeutic strategies for any biological profile. Particularly critic would be the implementation of systematic diagnostic screenings to identify early events and prevent the disease development into advanced primary and metastatic cancers for which the present therapies are still highly ineffective. This approach would provide the necessary information for optimized precision therapies and significantly decrease the social and economic burden of cancer. The progress pace will depend on the success in the identification of new biomarkers suitable for more precise tumor stratification and the successive development of reliable binders for selective recognition of tumor biomarkers on cells and in biological fluids. Affordable large-scale tests to detect early stage tumor in (risk) population will be however feasible if the diagnostic methodology will be not only reliable and sensitive, but also rapid, non-invasive, and inexpensive. In this perspective, Liquid Biopsy based on the evaluation of exosome biomarkers has the capacity to recapitulate the patient diagnostic status because this extracellular vesicle (EVs) class proved being involved in metastasis, and they are easily accessible in any body fluid. At the present, the technological limiting factor is the exosome purification protocol and our proposal aims at overcoming this bottleneck by developing antibodies for exosome immunopurification. Immunocapture is the method which provides the most pure exosome fractions and the only one available for separating extracellular vesicle sub-populations, such as tumor-specific exosomes from the “background” (physiological) exosomes present in biological fluids. Antibodies selective for exosome sub-populations will enable their fractionation and to evaluate separately their molecular content to identify the diagnostic relevant biomarkers. The exclusive recovery of tumor-related macromolecules will also contribute understanding the biological mechanisms by which exosomes participate into tumor progression, long-distance cell-to-cell regulation, and tumor microenvironment modifications. We have already demonstrated that recombinant antibody technology is suitable for the fast recovery of reliable anti-exosome binders and now propose the implementation of a platform for the production of an array of single-domain antibodies (also called nanobodies or VHHs) engineered for tumor diagnostic applications.
Significance for science
Scientific impact. The comparative analysis of the molecular content from different exosomes will provide basic research information useful to understand the biological mechanisms mediated by such vesicles; besides, valuable biomarkers for comprehensive diagnostics will be provided.
Social-medical impact. Large-scale population screening for different tumors will become feasible because we’ll have the biomarkers to look for and the reagents to perform the tests. The non-invasive liquid biopsy approach will make the procedure economically affordable and simpler for the patients. At the present, systemic surveys able to identify early tumor stage remain the most effective method to reduce cancer mortality.
Biotechnological and economic impact. The selected antibodies will be used to develop both immunoaffinity-based chromatographic systems and flow-cytometry-based diagnostic protocols. Both applications have a high commercial interest.
Biological impact. The possibility to obtain single EV sub-populations will finally enable their separate content analysis and the analysis of their biodistribution. This accomplishment will allow for the better understanding of the mechanisms by which exosomes accomplish their biological effects.
Significance for the country
Scientific impact. The comparative analysis of the molecular content from different exosomes will provide basic research information useful to understand the biological mechanisms mediated by such vesicles; besides, valuable biomarkers for comprehensive diagnostics will be provided.
Social-medical impact. Large-scale population screening for different tumors will become feasible because we’ll have the biomarkers to look for and the reagents to perform the tests. The non-invasive liquid biopsy approach will make the procedure economically affordable and simpler for the patients. At the present, systemic surveys able to identify early tumor stage remain the most effective method to reduce cancer mortality.
Biotechnological and economic impact. The selected antibodies will be used to develop both immunoaffinity-based chromatographic systems and flow-cytometry-based diagnostic protocols. Both applications have a high commercial interest.
Biological impact. The possibility to obtain single EV sub-populations will finally enable their separate content analysis and the analysis of their biodistribution. This accomplishment will allow for the better understanding of the mechanisms by which exosomes accomplish their biological effects.
Most important scientific results
Final report
Most important socioeconomically and culturally relevant results
Final report
