In this project we have studied the practical applicability of the ruthenium-based photoactivated chemotherapy (PACT) technology for the treatment of eye cancer, with a focus on uveal melanoma.
The work was realised in collaboration with Prof. Ewa Snaar-Jagalska from the Institute of Biology of Leiden University, and Prof. Martine Jager form the ophthalmology department of Leiden University Medical Center (LUMC).
The project entailed first a chemical part, looking at the development of a chromatography-free synthesis of this type of compounds, as a preparation to future GMP production.
The second and main part of the project was dedicated to testing a series of ruthenium-based PACT compounds in vitro and in vivo tumor models of uveal melanoma (UM), a rare tumor of the eye. We obtained a series of eye cancer cell lines from our collaborators, which allowed us to demonstrate the low toxicity in the dark, and high toxicity after light irradiation, of Ru-based PACT compounds on eye cancer cells in vitro. We then selected the most promising compounds and tested it on the one hand in zebra fish embryo tumor models, and on the other hand in mice tumor models. The biodistribution of this compound was studied for the first time in mice, which allowed to demonstrate the very fast blood clearance of this type of compounds. We also realised the first in vivo efficacy demonstration of a Ru-based PACT compound against both primary and metastatic uveal melanoma sub-cutaneous tumors in mice. One scientific article has been published on the zebra fish embryo work, and two articles on the mice study are being prepared and will be submitted in 2022. We also attracted a start-up with whom we prepared an EIC Transition proposal for further translational developments of this technology. We also communicated our results on social media, gave two oral contributions during the International Symposium on Occular Oncology, which took place in Leiden in June 2022, and presented a poster on the Gordon Research Conference on Metals in Medicine in Andover, USA.
We are currently looking for private investors who would be willing to fund further pre-clinical work and market developments of this technology, to realise the first clinical application of Ru-based PACT for the treatment of eye cancer.
