Homing peptides for targeted delivery of compounds across the blood-brain barrier (01.01.2018–31.12.2022)
Abstract: Our laboratory uses in vivo phage display to find homing peptides for systemic targeting of diagnostic and therapeutic payloads, primarily in the context of malignant disease. In our quest to target infiltrative glioblastoma (GBM) guerilla cells, which hide in the brain parenchyma behind highly impermeable blood-brain barrier (BBB), we became interested in exploration of the novel ways of delivering compounds to specific cell types in the brain. The goal of the current proposal is to develop peptide affinity ligands for targeting compounds (such as molecular and nanoscale sensors, actuators, and therapeutics) across the BBB to specific cells (including malignant cells) in the brain parenchyma. Improved affinity ligands crossing of the BBB would have broad applications beyond neuro-oncology, and allow non-invasive monitoring and/or activity modulation of specific cells and synapses in the mammalian brain e.g. in the context of neurodegenerative and neuro-inflammatory diseases.
Development of extracellular matrix-targeting precision cancer therapy (01.01.2020–30.06.2021)
Abstract: With the support of the EAG79 grant we performed comprehensive studies on preclinical development of the homing peptide that interacts with the extracellular matrix in solid tumors (proprietary PL1 peptide). Our results show that the bifunctional PL1 peptide, a platform technology for the development of tumour-specific molecular imaging and therapeutic conjugates, is superior to existing and emerging tumour-targeting payload-delivery strategies. With the support of the grant EAG79, we developed the system based on pprecision tumor delivery of drugs and companion imaging agents, and submitted the patent application to protect IP of the PL1 and related peptides in 2020 (International PCT No: PCT/IB2020/050847; Application Number: 62800879). The studies carried out with the support of the EAG79 grant form a backbone of the follow up European Innovation Council grant application (EIC transition grant, 2,5MEUR) on preclinical and clinical development of PL1 peptide that was submitted on September 22, 2021. This proposal will support establishment of a spin-off company of the University of Tartu (Precision Peptide Therapeutics) and international collaborative effort on translational development of PL1 guided drugs and contrast agents.
Precision targeting of infiltrative glioblastoma (01.01.2023–31.12.2027)
Abstract: Glioblastoma is the most aggressive form of primary brain cancer with no effective cure. In preclinical studies, homing peptide targeting ligands have proven useful in increasing accumulation of anticancer drugs in glioblastoma core lesions. However, new therapeutic paradigms are needed as the current peptides fail to target infiltrative “guerilla” malignant cells located away from tumor core behind the blood brain barrier. This project proposes interdisciplinary and translationally-oriented studies on identification and preclinical validation of homing peptides able to penetrate the blood brain barrier and to target infiltrative glioblastoma cells. The project will lead to identification and mechanistic characterization of the infiltrative glioblastoma targeting peptides and execution of the preclinical studies with peptide-guided therapeutic nanoparticles and radiotracers. These studies may lead to a new paradigm of peptide-based precision management of infiltrative glioblastoma.
