Tambet Teesalu

Development of tumor penetrating peptides for glioma targeting

The project aimed to tackle a key issue in solid tumor therapy: the limited penetration of anti-cancer drugs into tumor tissue and cells. The discovered tumor-penetrating peptides (TPP) enhance the penetration of drugs into tumors, improving their effectiveness. However, the current TPP primarily target angiogenic tumor vessels and may not be suitable for slow-growing or invasive tumors. The project team’s goal was to create glioma-specific TPP (gTPP) for delivering drugs to glioblastoma (GBM), a challenging brain tumor. GTPP is capable of penetrating gliomas, regardless of the angiogenic status, and delivering drugs to distant malignant cells. The team then optimised the platform for enhanced glioma drug delivery, paving the way for clinical trials.

Commercialising a novel glioblastoma targeted therapy and a companion diagnostic compound

Glioblastoma (GBM) is the most aggressive form of primary brain cancer, with an average survival of 12–15 months after diagnosis and less than 3–5% of patients surviving longer than 5 years. The main aim of the project was to probe the commercial viability of two types of tumor-targeted payload hybrids, one as an improved chemotherapeutic treatment, and the other as a precision-guided imaging agent for PET/MRI-based diagnosis. The goal of the project is for the former to become clinicians’ chemotherapy of choice in the adjuvant phase of GBM treatment, and for the latter to be incorporated into PET and MR-imaging procedures as a method for identifying and diagnosing GBM, as well as a companion test for stratification of patients for therapy.

Results

An important finding was that the team identified glioblastoma homing peptides that interact with the brain tumor extracellular matrix, the molecular “cement” where tumor cells reside. This matrix provides a high-capacity target for precision-guided delivery of drugs and nanoparticles. The team also identified peptides that target pro-tumorigenic immune cells in glioblastoma and other solid tumors. These peptides can modulate the tumor microenvironment to make it more responsive to immunotherapies. Additionally, the team improved the technology of in vivo peptide phage display, allowing unbiased, agnostic mapping of molecular differences in blood vessels in living organisms. This platform can be used for comprehensive mapping of “vascular ZIP codes” in health and disease in future studies.

Impact

Upon administration, drugs distribute throughout the body, not only at the site of disease. This limits their efficacy and results in unwanted side effects. The project team’s technology can make drugs “smart”, enabling them to recognise and preferentially accumulate at disease sites. This will potentially lead to better efficacy, fewer side effects, and cost savings. While the laboratory of the project team primarily develops smart drugs against cancer, the technology can also be applied to treat other diseases, particularly those with drug delivery challenges, such as brain diseases.