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Innovative Photoactivated Ruthenium Chemotherapy to treat eye cancer

Project description

Light-activated cure for rare eye tumour

Uveal melanoma, a rare eye tumour, robs patients of their sight. It also carries a grim 50 % mortality rate due to liver metastases. Current treatments exacerbate the issue, leading to a lower quality of life for those affected. In this context, the EIC-funded PACT4EYE project will introduce photoactivated chemotherapy (PACT) with a ruthenium-containing prodrug (Ru-MTI). This approach is activated by light. It aims to revolutionise uveal melanoma treatment. Unlike traditional treatments, PACT thrives in oxygen-deprived tumour tissues, enhancing efficacy. The project employs patient-derived models in zebrafish and mice to optimise treatment response and minimise systemic toxicity. With promising preclinical data, PACT4EYE sets the stage for attracting venture capital and funding agencies.

Objective

"Uveal melanoma (UM) is a rare tumor of the eye; its current treatment leads to lower quality-of-life for the patients (sight loss), 50% of whom eventually die from metastases to the liver. The PACT4EYE project aims at the first clinical development of a new technique called photoactivated chemotherapy (PACT) for the treatment of UM. It makes use of a new, patented ruthenium-containing prodrug (Ru-MTI) that must be activated by green or red light to become toxic. PACT uses laser light irradiation at the tumor site to activate the prodrug locally and destroy the tumor with low side effects for the patient. Its innovative mode of activation, based on a dioxygen-independent bond cleavage photoreaction, makes PACT treatment with Ru-MTI fundamentally different from state-of-the-art UM treatment that rely on O2 activation. Unlike them, Ru-MTI can still be activated in hypoxic tumor tissues, which are usually more resistant to existing treatment and more threatening for the patients. The consortium will screen and optimize the tumor response and systemic toxicity of PACT treatment with Ru-MTI in primary UM eye tumors and their liver metastases, using patient-derived tumor models engrafted in zebrafish embryos (ZF) and mice. Once the most responsive tumors are identified in ZF, the treatment will be optimised in sub-cutaneous mice models and further validated in an ""orthotopic"" mouse PDX model (for example, a liver metastasis in the liver), which represents one of the most predictive pre-clinical tumor models available to date. These results will allow our commercial partner to define a ""minimum viable product"" for PACT treatment of UM tumors with Ru- MTI, and to develop a business plan and a communication plan towards the first clinical application of ruthenium-based PACT. The project will gather all pre-clinical data necessary to convince venture capital and/or funding agencies to fund clinical phase I studies and further product development after the project."

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-EIC - HORIZON EIC Grants

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Call for proposal

(opens in new window) HORIZON-EIC-2023-TRANSITION-01

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Coordinator

UNIVERSITEIT LEIDEN
Net EU contribution
€ 1 021 623,75
Address
RAPENBURG 70
2311 EZ Leiden
Netherlands
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 021 623,75

Participants (3)