Innovative Photoactivated Ruthenium Chemotherapy to treat eye cancer

Introduction

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.

Project Aim

The PACT4EYE project aims at the first clinical development of a new technique called photoactivated chemotherapy (PACT) for the treatment of UM.

Treatment Mechanism

PACT makes use of a new, patented ruthenium-containing prodrug (Ru-MTI) that must be activated by green or red light to become toxic.

Activation Process

• 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 is based on a dioxygen-independent bond cleavage photoreaction, making PACT treatment with Ru-MTI fundamentally different from state-of-the-art UM treatments that rely on O2 activation.

Advantages of Ru-MTI

Unlike existing treatments, Ru-MTI can still be activated in hypoxic tumor tissues, which are usually more resistant to existing treatment and more threatening for the patients.

Research Methodology

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.

Optimization Process

1. Once the most responsive tumors are identified in ZF, the treatment will be optimized in sub-cutaneous mice models.
2. Further validation will occur 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.

Expected Outcomes

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.

Funding and Future Development

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.