Project description DEENESFRITPL Innovative 3D preclinical cancer model of brain metastases The EU-funded 3DBrainStrom project aims to establish 3D-printed models of brain metastases that include brain extracellular matrix, stroma and serum containing immune cells flowing in functional vessels. The models will better capture clinical tissue properties, signalling pathways, haemodynamics and drug responsiveness. The researchers will exploit the new models to design three therapeutic approaches to target cellular compartments involved in brain metastases: the prevention of brain metastatic colonisation using targeted nanovaccines; the inhibition of tumour–brain stroma cells crosstalk during micrometastases progression; and the selective targeting of tumour cells. The new preclinical cancer models will bridge the translational gap in cancer therapeutics. Show the project objective Hide the project objective Objective Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer. Fields of science medical and health sciencesmedical biotechnologynanomedicinemedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Topic(s) ERC-2018-ADG - ERC Advanced Grant Call for proposal ERC-2018-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator TEL AVIV UNIVERSITY Net EU contribution € 2 353 125,00 Address Ramat aviv 69978 Tel aviv Israel See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all TEL AVIV UNIVERSITY Israel Net EU contribution € 2 353 125,00 Address Ramat aviv 69978 Tel aviv See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
