Project: Proteomic screening of bronchoscopic biopsies-on-chip for improved prediction of anti-PD-1 responses in real-time.

Acronym	BronchoBOC (Reference Number: ERAPERMED2019-217)
Duration	01/04/2020 - 31/03/2023
Project Topic	Anti-PD-1 monotherapy first-line is indicated for patients with advanced non-small-cell lung cancer (NSCLC), accompanied by non-targetable driver mutations and >50% PDL1 expression. Still more than half of patients do not respond or become resistant after initial response. Identifying patients who will benefit from anti-PD-1 monotherapy or need more aggressive combinatorial therapy is an unmet need. Three-dimensional primary microfluidic cultures may capture the dynamic tumor-immune interplay and guide treatment through reverse translation. CCL19 and CXCL13 released in melanoma-derived microfluidic cultures correlate with clinical responses. Whether and how similar approaches can be applied to lung cancer, is to be defined. We aim to interrogate the applicability of an innovative 3D microfluidic device, i.e. organ-on-chip, in predicting real-time response to PD1-blockade in NSCLC patients. Bronchoscopic tumor biopsies are minimally invasive, routinely obtained from advanced NSCLC patients and are thus ideal for personalized drug screening. We will develop and validate the first bronchoscopic biopsies-on-chip (bronchoBOC). We will conduct a prospective multicentric exploratory co-clinical trial by studying in parallel clinical responses (complete/partial remission, progression, overall survival and progression-free survival) to a-PD1 monotherapy in treatment-naive advanced NSCLC patients (n˜48) matched to their bronchoBOCs. We will profile proteome responses to a-PD1 using mass spectrometry (LC-MS/MS), FACS, cytometric bead arrays, together with immunofluorescence and imaging. Artificial intelligence/machine learning approaches will be allied to bronchoBOC profiles and clinical data, to identify the best predictive biomarker patterns and validate them in a multi-feature model. The predictive model will be hosted in an easy to use interface to predict response to a-PD1.
Network	ERA PerMed
Call	2nd Joint Transnational Call for Proposals (2019)

Project partner

Number	Name	Role	Country
1	Biomedical Sciences Research Center (BSRC) Alexander Fleming	Coordinator	Greece
2	National and Kapodistrian University of Athens (UoA) Medical School and Evaggelismos Hospital	Partner	Greece
3	Institute of Virology (IVN)	Partner	Romania
4	Scientific Institute of Romagna for the Study of Cancer (IRST)	Partner	Italy
5	Emulate, Inc	Partner	United States
6	Mosaiques Diagnostics	Partner	Germany
7	Careggi Univerity Hospital (AOU Careggi), Firenze	Partner	Italy