Periodic Reporting for period 5 - Lumiblast (A paradigm shift in cancer therapy – using mitochondria-powered chemiluminescence to non-invasively treat inaccessible tumours) Reporting period: 2022-04-01 to 2023-01-31 Summary of the context and overall objectives of the project • What is the problem/issue being addressed?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. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The work in LUMIBLAST is currently under a restrictive supply of information. This is for the benefit of the potential application in the sense that if protected then industrial partners will in the future have the incentive to finance and promote LUMIBLAST into the clinic. In this context there is currently an “embargo” in the flow of information which will be gradually lifted upon successful patenting of LUMIBLAST. The first LUMIBLAST patent has been published, but a new one is now necessary to protect all the LUMIBLST derivatives. In this context also, the dissemination of results has to be limited for the time being and we cannot go out fully to the end and lead users as we would have liked to. However, here is some information on the workflow so far: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 Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The project has, so far, progressed beyond the state of art as we have provided proof of principle of a technology never validated before. Apart from the central idea however, the chemical synthesis has also progressed beyond the state of art and also the photo-physical/chemical studies have produced novel results. Lumiblast, provided employment to 6 full time new researchers plus a variable number of part-time PhD students and technicians (part-time or in kind), and has benefited much the labs involved in growth and research. Also the project has created a new scientific network of labs with direct access to one another for the collaboration on other projects non-related to LUMIBLAST or for the design of future collaborative research. Through these collaborations there are some early commercial initiatives between partners from the academia and industry for the launching of new products and this initiative might even seek support from the FET OPEN launchpad scheme. By the end of the project, we have very positive in vitro results for 3 Lumiblast compounds and also very encouraging results from the xenograft GBM studies on mice. We are trying to secure the funds for translating our project further, mainly through the EIC transition grant scheme. lumiblast-illustration.png
