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High-performance biomechanical model of combined immunotherapy and anti-angiogenic cancer treatment

Project description

The vascular road to effective immunotherapy

Tumour growth and treatment delivery are highly dependent on vascularisation of the tumour itself. Tumour cells produce molecules that encourage angiogenesis, supporting their rapid growth and transition from benign tumours to malignant. These molecules also make the blood vessels leaky and porous. The latter helps tumour cells to enter the bloodstream and spread while concurrently compromising delivery of chemo- and immuno-therapies. EU-funded scientists are developing computational models of tumour microenvironments and repair of vascular abnormalities to better understand the effects of optimised vascular perfusion on promising immunotherapies. Predictions will be tested in experimental models.

Objective

Inefficient delivery of cellular and molecular medicines to solid tumors can reduce dramatically the efficacy of treatment and affect negatively patient’s survival. This explains in large part why standard chemo- and immune-therapies often fail to treat specific cancer types, even though these therapies are potent enough to eradicate cancer cells. Abnormalities in the structure of the tumor vasculature hinder tumor perfusion and as a result the systemic delivery of the medicines. In many tumor types, blood vessels are hyper-permeable, leaving large interendothelial openings, which causes fluid loss from the vascular to the interstitial tumor space. Vessel hyper-permeability can reduce tumor blood flow, rendering tumors hypo-perfused and hypoxic. Impaired blood supply and hypoxia help cancer cells evade the immune system and increase their invasive and metastatic potential. Normalization of the tumor vasculature is a clinical strategy to repair vascular abnormalities in order to improve perfusion, oxygenation and delivery of medicines. Immunotherapy is gaining interest as an effective therapeutic approach against cancer, but only a subset of patients receiving immunotherapy exhibit sustained tumor shrinkage. Here, we hypothesize that vascular normalization can improve immunotherapy. The objective of the proposed research is the optimal design of the combined immunotherapy and vascular normalization therapeutic approach. To this end, a numerical and experimental study is proposed to model and experimentally validate the vascular normalization procedure, focusing on its combined effects with immunotherapeutic drugs. The proposed research/training will complement the Applicant’s skills in high-performance computing, advanced optimization algorithms and artificial neural networks with the Host’s expertise in tumor microenvironment and cancer drug delivery to enhance his professional maturity and promote international collaborations.

Call for proposal

H2020-WF-2018-2020

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Sub call

H2020-WF-01-2018

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Coordinator

UNIVERSITY OF CYPRUS
Net EU contribution
€ 145 941,12
Address
Avenue panepistimiou 2109 aglantzi
1678 Nicosia
Cyprus

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Region
Κύπρος Κύπρος Κύπρος
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00