Periodic Reporting for period 5 - Lumiblast (A paradigm shift in cancer therapy – using mitochondria-powered chemiluminescence to non-invasively treat inaccessible tumours)
Période du rapport: 2022-04-01 au 2023-01-31
LUMIBLAST started on the 1st October 2016. The overall aim of the project is to address deep lying cancers like brain cancers (e.g. glioblastoma multiforme – GBM) by using chemically generated intracellular light to excite a photosensitive drug and consequently kill the tumour around it by generating toxic oxygen byproducts.
• Why is it important for society?
Cancers like GBM are practically incurable due to their location and their highly aggressive nature. While the GBM standard of care (surgery, radiotherapy, and chemotherapy) can slightly prolong the patents' survival median from ~3 to ~15 months, it cannot provide a curative solution. By contrast, the fluorescence of GBM-specific 5-ALA-derived protoporphyrin IX (PpIX) is currently used intraoperatively to guide the precise resection of the cancerous tissues. This specificity makes GBM photodynamic therapy (PDT) an attractive solution, however its application faces two problems: i) Light accessibility without surgical intervention and ii) inability to eradicate all the tumour cells, due to the limited penetration of light into tissue.
Lumiblast which is in practice a form PDT from within the cell, using chemiluminescence instead of an external light source (e.g. lamp or laser) can prove either curative or able to provide a long term management of the disease providing the patients with a substantial prologation of life.
• What are the overall objectives?
The overall project objectives are:
- Design and synthesis of the LUMIBLAST compounds with varying properties.
- Photochemical studies on the LUMIBLAST compounds, with regards to their stability, luminescence efficiency and ability to interact with photosensitive dugs and provide them with light.
- Validation and optimization of LUMIBLAST in GBM cancer cell lines, and selection of the best perform-ing modified luminols for animal studies (WP3).
- Evaluation of LUMIBLAST in the appropriate animal tumour models.
- Assessment of LUMIBLAST potential towards a clinical application based on the project results and design of a tentative business plan.
Up to now all the chemiluminescent compounds have been synthesized and have been tested for their luminescence and photochemical properties, but also for their efficacy with GBM cells in culture. This work has led to the identification of the most promising candidates for animal experiments. Indeed, selected compounds have been tested on preclinical GBM xenograft models. The ethical consent for experiments on orthotopic animal models has now been obtained and work is in progress for the setup of the stereotaxic system and the commencement of the orthotopic work. After the establishment of the stereotaxic system, the ethical approval application for orthotopic studies was submitted to both local and national authorities in Norway. establishment of orthotopic models took place from September 2022 to January 2023, while the application for ethical approval on the efficacy orthotopic was approved for submission to the national authorities on 2nd February 2023 after a long consultation with the local authorities