Summary
Molecular screening for solid tumors aimed at early detection of the disease and monitoring for the appropriate therapeutic choice has, to date, only been implemented in some types of cancer, with limited effectiveness. Currently recognized screening solutions are not applicable to most tumors. Therefore, the definitive diagnosis of cancer occurs only through invasive and expensive methods (example: endoscopy and imaging), typically applied to patients in an advanced stage of the disease in whom they present significant symptoms. Diagnosis of cancer via tissue biopsy involves invasive procedures, high overall costs for the national healthcare system, and limited accuracy because it is subject to intra-tumor heterogeneity. Co-morbidity, uncertain and/or overlapping symptoms represent the current challenge, which existing screening methods cannot support. EVs released by the tumor are one of the main recognized sources of surrogate tumor markers that allow diagnostic information to be extracted in a non-invasive, timely and "cost-effective" manner. The isolation and analysis of circulating EVs therefore constitutes a 'key enabling technology', i.e. the technology that, in the near future, will make precision diagnostics possible. In particular, EXI and ISS have identified a series of antigens on the surface and/or contained in exosomes of tumor origin, among which there are proteins involved in the 'pathways' most adopted in tumors ("tumor hallmarks", for example metabolism and interaction with the microenvironment), or recognize a phosphorylation state indicative of tumor pathogenesis. The EVEarlyPannel project aims to enhance assays by bringing them towards the second generation of prototypes, equipped with additional biomarkers/antibodies and testing them in a validation context realistically close to screening conditions for early diagnosis and predictability of therapeutic response. The test will be made highly specific and sensitive thanks to the use of ad hoc conjugation protocols and materials, combined with innovative signal detection systems implemented in an enhanced ELISA assay ('enhanced' or 'digital'), in immuno-NGS or through droplet digital PCR. These analytical platforms have now entered "routine" clinical practice and the combination with new generation molecular and analytical tools for the early diagnosis of tumors in liquid biopsy makes this technological approach very promising for screening and monitoring in oncology.
Purpose
Our strategic plan includes the advanced development and beta testing of new products (IVD assays for screening and IVM for monitoring), and services (validation of biomarkers and development of companion diagnostics) aimed at the academic, clinical and large pharmaceutical companies. The aims of the project include: 1) promoting the acquisition of new skills and the effective transfer of research results both in the academic and industrial fields into commercially viable products; 2) promote the integration of exosomal diagnostics in the management paths of the cancer patient in the phases of diagnosis and attribution of the right treatment: in fact, within the scope of this project, clinical trials aimed at guaranteeing the compliance of diagnostic products and services with the regional, national, European (and beyond) regulatory standards that allow the rapid adoption of the new test in healthcare systems. The proposal for validation in oncology niches currently without diagnostic tests (high-risk categories) and the proposal for classification as complementary tests to the tests already in use, together with an accuracy and cost profile of our products, will facilitate the registration process and market positioning; 3) generation of an economic impact that includes the return of investments to the lead company, export of products and services not limited to regional and national markets and savings on the part of the national healthcare system thanks to the consequent optimization of diagnostic pathways during surveillance and treatment of cancer patients; 4) integration and convergence of public and private structures in a new "hub" of excellence that offers services to the world of basic and clinical research, and contracts with "Pharma", whose overall value exceeds the wealth of skills of the individuals participants. Strengthening existing relationships between project partners will make translational and regulatory efforts effective in particular for participating companies, will shorten the time needed to reach the market and will increase the appeal for new strategic ('corporate') or 'venture' investors. '.
Final goal
The project is part of the development of liquid biopsy assays for diagnostic and therapeutic response predictive approaches in the oncology sector where effective screening methods are currently not available. The general objective is to qualify and validate the diagnostic usefulness and added value, compared to the solutions currently used in clinical practice, of innovative methods and prototype kits for in vitro diagnostics and monitoring (IVD and IVM) for characterization of circulating tumor extracellular vesicles (EVs), in particular exosomes, as a triage tool for the timely and accurate identification of diseased subjects within populations at high and medium risk for developing cancer or developing aggressive forms and to assign the right therapy. The project aims to cooperate in developing and perfecting a non-invasive diagnostic and predictive monitoring "tool", easily transferable within the national healthcare system. For this purpose, the pre-existing intellectual property and the 'know-how' of the individual proponents are valorised, and the investments previously made in the identification and preliminary validation of the "tools" which represent the current starting point of the EVEarlyPannel project. The experimental plan is consistent with the mission of ISS and UniCatt and with an ongoing industrial plan, approved by the respective board of the participating lead company. Finally, the clinical validation trial is expected to identify the prototype test format with the correct accuracy, complexity and cost profile capable of facilitating the process of registering and positioning a new CE-marked test on the market and starting the dialogue and/or open the file for approval by the "Food and Drug Administration" (FDA), leading to the consolidation of the lead company in the role of world leader in the field of liquid biopsy and oncological screening.
