Periodic Reporting for period 1 - BuonMarrow (Bone Marrow-on-Chip as smart sensor of lung cancer relapse)
Período documentado: 2024-03-01 hasta 2025-02-28
In the past 40 years the overall survival rate for people affected by tumors has doubled, with about 50% of patients now surviving their disease for 10 years or more. Nonetheless, some cancers (e.g lung cancer) still have poor survival rate. A major cause of lung cancer mortality is represented by disease relapse, occuring when few of the original cancercells survive the initial treatment and causing primary tumor recurrence. Currently, no options are available to predict the risk of lung cancer relapse, which is only diagnosed late based on radiological evidence. Hence, the ability to early detect lung cancer relapse represents an urgent and unmet need, since a fast and tailored treatment could dramatically increase patients’ survival rate.
BuonMarrow lays on the groundbreaking hypothesis, supported by our Consortium preliminary clinical evidence, that bone marrow mesenchymal stromal cells (BM-MSC) may be educated upon cancer mediators exposure, and acquire a long-term memory-like response which is amplified when exposed to a secondary tumor. Owing to breakthrough technologies available in the Consortium (organ-on-chip, innovative optical sensors and biological modeling of the bone marrow niche), BuonMarrow partners will develop an in vitro miniaturized bone marrow device able to harness the amplified BM-MSC response generated by liquid biopsy of lung cancer patients, thus acting as a biological sensor for the early detection of relapse. A combination of retrospective and prospective clinical studies, respectively, will allow to calibrate and validate such sensor, delivering an unprecedented tool to assist the decision-making process on lung cancer patients.We expect to significantly improve oncological treatments, building on a personalized medicine approach to increased patient survival and well-being, and thereby deeply impacting on EU’s socio/economic environment.
BuonMarrow lays on the groundbreaking hypothesis, supported by our Consortium preliminary clinical evidence, that bone marrow mesenchymal stromal cells (BM-MSC) may be educated upon cancer mediators exposure, and acquire a long-term memory-like response which is amplified when exposed to a secondary tumor. Owing to breakthrough technologies available in the Consortium (organ-on-chip, innovative optical sensors and biological modeling of the bone marrow niche), BuonMarrow partners will develop an in vitro miniaturized bone marrow device able to harness the amplified BM-MSC response generated by liquid biopsy of lung cancer patients, thus acting as a biological sensor for the early detection of relapse. A combination of retrospective and prospective clinical studies, respectively, will allow to calibrate and validate such sensor, delivering an unprecedented tool to assist the decision-making process on lung cancer patients.We expect to significantly improve oncological treatments, building on a personalized medicine approach to increased patient survival and well-being, and thereby deeply impacting on EU’s socio/economic environment.
In the first year of activities, technological platforms have been implemented to generate bone marrow-on-chip models, featuring mechanical stimulation and biosensing capabilities. Microfluidic bioareactors have been developed to optimize culture conditions of MSOD and MSOD-B cells (as standardized cellular model of the mesenchymal stromal/stem cells) as well hematopoietic stem cells (HSC) from human cord-blood. Co-culture experiments have also been carried out to better mimic the native hematopoietic stem cell niche. Biosensors have been developed to quantify the concentration of cytokines (e.g. IL1ß) released by the bone marrow-on-chip upon stimulation with factors present in the tumor patients plasma.
In parallel, the enrollment of prospectively lung cancer (LC-P) patients have started with the collection and analysis of their peripheral blood mononuclear cells (PBMC) samples. So far, 19 patients have been enrolled in the T0 time point. Concerning BM-MSCs education, we compared patient plasma and extracellular vesicles (EVs) for capacity to induce memory responses in MSOD cells. Results showed that EVs extracted from the plasma of lung cancer patients are the relevant mediators of BM-MSCs education/training, which has been assessed as a boost in the production of known immunological mediator upon BM-MSCs restimulation with EVs.
In parallel, the enrollment of prospectively lung cancer (LC-P) patients have started with the collection and analysis of their peripheral blood mononuclear cells (PBMC) samples. So far, 19 patients have been enrolled in the T0 time point. Concerning BM-MSCs education, we compared patient plasma and extracellular vesicles (EVs) for capacity to induce memory responses in MSOD cells. Results showed that EVs extracted from the plasma of lung cancer patients are the relevant mediators of BM-MSCs education/training, which has been assessed as a boost in the production of known immunological mediator upon BM-MSCs restimulation with EVs.