The diagnostic kit (LCC Diagnostics) has been tested in a broader set of brain tumor patients. Patient specific categories with tumor-specific entities that would benefit from diagnosis have been identified. In detail, both pediatric and adult brain tumor cells have been identified that are specifically vulnerable to our therapeutic invention for LCC Therapeutics. Preliminary data from using LCC Diagnostics show that our target is upregulated after standard treatment (standard irradiation or standard cytostatic drugs for both pediatric and adult brain tumors). Cell culture experiments has identified detailed ratios and more precise magnitudes of increased levels from our reporters (in the LCC Diagnostics kit). An estimation of the increased risk for brain tumor relapse has been clarified from using the diagnostic kit in careful experimental settings. We have started to set up standard routines and defined criteria for the collection of patient samples from operation.
The therapeutic kit (LCC Therapeutics) has been developed with different promoters. Proof of concept studies have been performed to evaluate the pros and cons of various promoters. A minimal promoter has been selected to drive herpes simplex virus HSV-TK expression in LCC Therapeutics. This promoter is optimal to use for selective killing of cancer cells as expected. LCC Therapeutics has been tested for efficacy in vitro and in animals in vivo. In mice it was found to have great efficacy in both pediatric and adult brain tumor cells after infecting cells with the gene therapy. Following 10 days of ganciclovir treatment that turn on LCC Therapeutics (that acts like a Trojan Horse) will significantly eradicate SOX9-positive tumor cells. Here, tumor growth is suppressed (inducing cell death of tumor cells) and mice consequently survive significantly longer. We further tested 20 days of ganciclovir treatment, experienced even better survival differences and still found no side effects (no weigh loss or apparent sickness) from treatment. The scientific discoveries were summarized in a manuscript that will be submitted for publication before the summer of 2024.
An international patent application was submitted in August 2021 and was published in March 2022, before this project started. Patenting applications for national approval were initiated in late 2022, which was fully supported by this ERC PoC project. Here, we have according to our project proposal consulted a European patent attorney in Stockholm, Sweden, and during 2023 we sent in revised national patent applications to EPO, USPTO, Canada and as well a PCT National Phase entry in Australia and Canada.
A business model has been written together with a business advisor, with a first target product profile (TPP) attachment for the invention with details on intended use, target populations (relapsing malignant brain tumors with a focus on relapsed glioblastoma patients) including safety and efficacy-related characteristics of our gene therapy. Estimated costs future clinical trials have been proposed after meetings with companies (SMEs) experienced with similar gene therapy projects. We have had meetings with manufacturing companies that can perform GMP-production of our gene therapy LCC Therapeutics. Estimated costs for the full manufacturing to first clinical trials has been clarified. A rough but pragmatic estimate of further investments needed has been made and included in our business plan.
Finally, we ordered and tested a number of AAV serotypes that can facilitate LCC Therapeutics delivery in the brain. Therefore, high grade viral titers of the most promising AAVs were cloned and ordered. Before the project was completed, an AAV2 version of LCC Therapeutics was tested in vitro. It was found to work well and could specifically eradicate latent brain tumor cells. We presented the data to a local investor coupled to our university. The investor company was convinced by our results and has now supported this project where AAV2 LCC Therapeutics will now be tested in vivo and a regulatory strategy for the therapy towards future clinical trials for glioblastoma patients will now be initiated.
In summary, the ERC PoC project has been carried out as expected.
