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VAScularised Tumour Organoids on a chip with human placenta vessels as a preclinical model for anticancer therapies.

Project description

A microfluidic platform for testing CAR-T cell therapies

Tumour organoids have emerged as promising models for testing anti-cancer therapies as they offer a realistic representation of tumour architecture and behaviour. However, they usually lack functional blood vessels that are properly connected and perfusable. This is a key limitation when trying to study interactions between tumours, immune cells and therapies in a realistic setting. The goal of the ERC-funded VASTO project is to develop a novel microfluidic-based platform for studying the efficiency of CAR-T therapies. Unlike traditional microvascular models which rely on in vitro-grown endothelial cell layers to mimic blood vessels, VASTO researchers propose to use ex vivo human blood vessels to recreate the tumour microenvironment.

Objective

VASTO Proof of Concept aims to develop and test an innovative microfluidic-based platform, which allows to evaluate the efficacy of different cell immunotherapy strategies against solid tumours. For this aim, we propose to microfabricate 3D solid tumour organoids with an aberrant microvascular network provided from the explant of human vessels. Although there are other different vessel-on-a-chip and/or microvascular network formation approaches that use in vitro cell monolayers, we are not aware of any solution covering human ex vivo blood vessel platform as it is proposed here. Therefore, we aim to recreate the existent mechano-chemical barriers characteristics of the tumour microenvironment in solid tumours with this novel ex vivo platform.
With this technology, we can define a method to evaluate the efficacy of different immunotherapy-based strategies. Specifically, we focus on studying the effectivity of different Chimeric Antigen Receptor (CAR)-T cell therapies in solid tumours. Hence, the development of VASTO harbours the interest of CAR-T manufacturers to test these cell therapies against solid tumours. We will be able to asses CAR-T cell vascular extravasation, penetration into solid tumours and the CAR-T efficiency for tumour elimination.
In addition to its applicability to liver cancer, the acquired knowledge in VASTO also could be extrapolated to any other kind tumours, but also in the development of an ex vivo platform for research in regenerative processes, by incorporating organoids from healthy donors, instead of malignant cells, and promoting functional vasculature, instead of aberrant one.
Therefore, this human ex vivo platform will launch a new product to the market very attractive for clinical labs and companies, reducing animal experiments and providing a more reliable alternative for testing different therapies against tumours and approaching a more personalized patient-like model.

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2023-POC

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Host institution

UNIVERSIDAD DE ZARAGOZA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 130 000,00
Address
CALLE PEDRO CERBUNA 12
50009 ZARAGOZA
Spain

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Region
Noreste Aragón Zaragoza
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (2)

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