Objective This application addresses a major problem in therapy of solid tumors: poor penetration of anti-cancer drugs into tumor tissue and to infiltrating tumor cells. Recently, we have identified tumor penetrating peptides (TPP) that trigger specific penetration of co-administered un-conjugated drugs deep into tumor and increase their therapeutic index. Current TPP target angiogenic tumor vessels and may not be suitable for targeting slow-growing tumors and invasive tumor cells. TPP are composed of functional modules (tumor recruitment motif, cryptic tissue penetrating C-end Rule element, and a protease cleavage site), which can be rearranged to yield peptides of novel specificities.Our goal is to develop TPP platform for delivery of co-administered drugs to the deadliest brain tumor – glioblastoma (GBM). High-grade glioma is a target that is particularly evasive and well-suited for tissue penetrative drug delivery. We will develop glioma-specific TPP (gTPP) by combination of in vivo and ex vivo phage display of constrained peptide libraries on state-of-the-art glioma animal models. These gTPP will be able to penetrate gliomas (and potentially other tumors) independent of their angiogenic status, and to deliver drugs to infiltrating malignant cells far from the bulk glioma lesion. We will characterize, validate, and optimize the gTPP platform for enhanced glioma delivery of co-injected drugs. These studies will provide the preclinical data needed to advance the gTPP combination therapy of glioma to GLP toxicology and subsequent IND filing. Fields of science natural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesmedical and health sciencesbasic medicinetoxicology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator TARTU ULIKOOL Address Ulikooli 18 51005 Tartu Estonia See on map Region Eesti Eesti Lõuna-Eesti Activity type Higher or Secondary Education Establishments Principal investigator Tambet Teesalu (Mr.) Administrative Contact Kadri Raav (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all TARTU ULIKOOL Estonia EU contribution € 1 499 931,00 Address Ulikooli 18 51005 Tartu See on map Region Eesti Eesti Lõuna-Eesti Activity type Higher or Secondary Education Establishments Principal investigator Tambet Teesalu (Mr.) Administrative Contact Kadri Raav (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
