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3D Metastatic Tumor Model Coupled with Targeted mRNA Immunotherapy for the Effective Management of Breast Cancer Brain Metastases

Project description

Therapy for breast cancer metastases in the brain

Breast cancer metastases in the brain are common yet remain difficult to treat due to late diagnosis and the blood-brain barrier. With conventional therapies like chemotherapy and radiotherapy offering limited success, there is a need for novel treatments capable of reaching the brain. With the support of the Marie Skłodowska-Curie Actions programme, the 3DMETACARE project will develop a novel mRNA-based immunotherapy using lipid nanoparticles. These nanoparticles will be functionalised with mannose on their surface to facilitate delivery across the blood-brain barrier. Testing will take place in ex vivo 3D models of breast cancer metastases in the brain. This interdisciplinary approach aims to improve diagnosis time, therapy evaluation, and treatment outcomes in metastatic breast cancer.

Objective

Breast Cancer Brain Metastases (BC-BM) signifies second most common (30%) among all cancers, majorly effecting women population in the age group 45-69, and almost 40% of BC patients have been diagnosed with BC-BM during BC disease conditions. Conventional BC-BM management (chemo + radiotherapy), despite of progression into loco-regional therapies, have showed major limitations for effective management of BC-BM includes blood–brain barrier (BBB) in brain and substantial diagnosis at preliminary stage of disease. In last two decades several pre-clinical and clinical investigations of BC vaccines based on tumour-associated antigens and tumour-specific antigens approaches but none of the has been approved for either treatment or prevention. However, messenger RNA (mRNA)-based vaccination has the potential to expand the responders using targeted lipid nanoparticles (LNP) to counter challenging tumor microenvironment (TME) and BBB obstacles for metastatic tumour. Thus, 3D-METACARE will be focused on the fabrication of targeted LNP-HER2+mRNA immunotherapy decorated with mannose to effectively target Macrophage mannose receptor 1 with improved permeation through BBB and will target BC-BM. Followed by, robust 3D spheroid (cancer cell lines) and organoid (cancer tissues) model of BC and BC-BM, respectively will be established as effective preclinical models for understanding metastatic behaviour of HER2+ cancer and screening of anticancer therapies. Further, in-vitro 3D models will be conjugated with modified Raman spectroscopy techniques (SERS, CARS and SERM) for quantitative determination of the immunotherapeutic impact (T cell analysis) of LNP-mRNA in the ex-vivo BC and BC-BM models and metabolic activities in the native TME. Overall, 3DMETACARE will be novel interdisciplinary (nanotechnology+bioengineering+photonics) platform converging on current EU’s leading cancer research priorities such as early diagnosis and targeted therapeutics.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITY OF LIMERICK
Net EU contribution
€ 268 568,64
Address
NATIONAL TECHNOLOGICAL PARK, PLASSEY
- Limerick
Ireland
Region
Ireland Southern Mid-West
Activity type
Higher or Secondary Education Establishments
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Total cost
No data