Glioblastoma (GBM) is the most aggressive form of primary brain cancer with no effective cure. An important cause of the ineffectiveness of the GBM treatment lies within the chemotherapy component of the regimen, in that the systemically-delivered drugs are inefficient in accumulating at and penetrating tumor lesions. With the support of the ERC PoC grant GLIOGUIDE, we developed PL1, a unique bispecific homing peptide that selectively targets tumor-associated extracellular matrix, homes to GBM tissue and penetrates the tumor with high specificity, as a targeting ligand for delivery of payloads to GBM lesions. In particular, GLIOGUIDE-supported activities explored the translational potential of PL-1 guided diagnostic therapeutic for GBM and supported critical first steps on en route to market.
In GLIOGUIDE-supported Proof-of-concept studies, we developed two types of tumor-targeted PL1-payload hybrids, one as an improved anticancer treatment, and the other as a precision-guided contrast agent for imaging-based diagnosis and patient stratification. The goal was for the former to become the clinician’s chemotherapy of choice in the adjuvant phase of GBM treatment; and for the latter to be incorporated into MR-imaging procedures as a method for identifying and diagnosing GBM, as well as a companion test for stratification of patients for PL1-based therapy. These proof-of-concept studies were accompanied by activities on (1) IP and regulatory preparation and submission, and (2) commercial feasibility assessment.
The proposed work has validated the GBM-targeting characteristics and translational potential of PL-guided imaging and therapeutic compounds for improved glioma detection and treatment. At the current stage we are working on additional Investigational New Drug (IND)-enabling studies to develop PL1-guided compounds towards clinical applications.
