Project Name: Brain tumor penetrating peptides
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, 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). 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 independent of their angiogenic status, and to deliver co-administered drugs to infiltrating malignant cells far from the bulk glioma lesion.
Demonstration that the penetration of anti-cancer agents to glioma lesions can be specifically increased would be an advance of broad ramifications. First, more drug (or diagnostic probe) can be delivered into a glioma than in a standard regimen. Second, the procedure can help solve the tumor penetration problem by reaching the infiltrative glioma cells that cannot be accessed with conventional delivery. Third, the gTPP will provide an angiogenesis-independent paradigm of tumor penetrative delivery that can be potentially applied to other types of solid tumors. Finally, as the drug does not have to be conjugated to the peptide, once a gTPP has been clinically validated, it can be used to augment the efficacy of any imaging agent or anti-cancer drug - a major advance in glioma therapy could ensue.
The gTPP delivery system may therefore represent a paradigm shift in glioma drug delivery.Annotation: