Research topics/Work packages
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.
WP1: Upscaled drug synthesis
Objectives
- Develop a chromatography-free synthesis of Ru-MTI, upscale to 10g, and analyze production costs
WP2: Screening and optimisation of PACT treatment with Ru-MTI
Objectives
- O2.1 Screen antitumor efficacy and toxicity of PACT treatment with Ru-MTI in different genetic variants of UM utilizing UM ZF-PDX models
- O2.2 Optimize treatment in sub-cutaneous UM M-PDX models
WP3: Validation of PACT treatment with Ru-MTI in orthotopic mice models
Objectives
- O3.1 Validate orthotopic murine UM eye tumor and liver metastasis models
- O3.2 Validate PACT treatment of UM with Ru-MTI in orthotopic mice models
- O3.3 Study toxicity and eye toxicity of PACT treatment with Ru-MTI in healthy mice and in orthotopic mice tumor models
WP4: Development of the minimal viable product C-light for human use
Objectives
- O4.1 Integrate experience from previous commercialization, pre-clinical testing (WP2-WP3), and discussions with KOLs and industrial partners
- O4.2 define and develop C-light