START is based on an Italian patent that concerns the therapeutic use of CD99-null extracellular vesicles and their pharmaceutical composition. In the project, CD99-null vesicles alone or in combination will be tested against Ewing sarcoma, a rare pediatric bone tumor with very limited therapeutic options for patients who do not respond to standard drugs. 

The project applies cutting-edge technologies (large-scale drug screenings (HTS); patient-derived xenografts and Zebrafish models; single-cell and spatial transcriptomics) to gain in-depth knowledge of the efficacy of these vesicles against a solid tumor. The effects generated in recipient cells, whether tumoral or normal, will be analyzed and the frequency of administration, as well as the best route of administration to obtain therapeutic effects, will be evaluated. 

The project also addresses issues related to the standardization of processing and storage of CD99-null vesicles in order to ensure product compliance and traceability, in view of its potential clinical use. 

Four IRCCS partecipate to the project: 

• IRCCS Istituto Ortopedico Rizzoli
• Istituto Nazionale Tumori IRCCS "Fondazione G.Pascale"
• IRCCS Istituto Tumori Giovanni Paolo II
• IRCCS Istituto Romagnolo per lo Studio dei Tumori"Dino Amadori"

The PI of the study is Dr. Katia Scotlandi, head of the SSD Laboratory of Experimental Oncology. The following principal investigators participate to the study: 

• Dr. Marco Gambarotti, head of the SSD Pathological Anatomy and co-PI of the project
• Dr. Gianluca Giavaresi, acting head of the SC Surgical Sciences and Technologies
• Dr. Alessandra de Feo, a young researcher of the Laboratory of Experimental Oncology

The project was funded thanks to the Proof of Concept PNRR call, which, within the framework of the National Recovery and Resilience Plan, financed programs for the valorization of patents or patent applications held by entities belonging to the research world. 

• Italia Domani, il Piano Nazionale di Ripresa e Resilienza
• PNRR - Salute

The Rizzoli-Sicilia Department of Bagheria made an operation to remove a primitive tumor, a sarcoma of Ewing, in a patient of pediatric age.

"Anna will turn 14 tomorrow, March 8, today was the first post-operative check-up and to give her and her family the news of the how the surgery went well. This for us is the greatest professional and human gratification" says Toscano.

The researchers, led by Dr. Katia Scotlandi, head of the Laboratory of Experimental Oncology at the IRCCS Orthopedic Institute Rizzoli, have identified an unprecedented function of the CD99 antigen. 

Research project about Ewing's sarcoma, one of the most common primary bone tumors and mainly affects children and young adults.

It is a tumor which, despite the efforts made, still has cognitive and clinical needs to solve, and requires a research path in order to improve patient care, with particular attention to the more aggressive forms.

The project investigates molecules (RNA/proteins) hypothesized as the main responsible for the dynamics associated with the metastatic process.

Through the use of preclinical models capable of representing the genetic and epigenetic complexity of human Ewing's sarcoma, the project aims to study the processes that regulate the trafficking, localization and function of these molecules both at the intracellular level and within of extracellular vesicles, in order to identify new therapeutic targets.

The ultimate goal is the definition of new pharmacological treatments to be offered to oncologists who treat patients with this pathology

Project: AIRC - Accelerating biomarkers and targeted therapy development in metastatic Ewing sarcomas: focus on tumor cell plasticity.

Acronym: AIRC IG2019 Id22805

Call: Investigator Grant - IG 2019 YEAR 2019

Funding body: FONDAZIONE AIRC

Duration: 01/01/2020-01/04/2025

Principal Investigator: Katia Scotlandi

Total funded: 1.050.000,00€