Cyclized NGR Peptide for Tumor Targeting

Available for licensing and commercial development are patent rights and materials related to NGR peptides for targeting therapeutic and diagnostic agents to cancer cells. Specifically targeted are tumors that express aminopeptidase N isoform CD13. NGR peptides include the Asn-Gly-Arg peptide motif, a ligand for APN/CD13. NGR-containing peptides have been proven useful for delivering cytotoxic drugs, apoptotic peptides, and cytokines (such as tumor necrosis factor (TNF) to tumor vasculature. In some embodiments of the invention, the NGR peptide is conjugated with a diagnostic moiety such as a fluorophore, nonmetallic isotope, an optical reporter, a boron neutron absorber, a paramagnetic metal ion, a ferromagnetic metal, a gamma-emitting radioisotope, a positron-emitting radioisotope, or an x-ray absorber. In another embodiment, the peptide can be conjugated with a therapeutic such as daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, or a combination of these. The therapeutic agent, such as an anti-tumor or anti-neoplastic agent of choice, can be entrapped within a liposome; the liposomes are formulated to be of a size known to penetrate the endothelial and basement membrane barriers. The resulting liposomal formulation can be administered parenterally to a subject in need of such treatment, preferably by intravenous administration. Tumors characterized by an acute increase in permeability of the vasculature in the region of tumor growth are particularly suited for treatment by the present invention.

Illustration of exemplary molecule:conjugated fluorophore

Figure 1. Illustration of exemplary molecule: Conjugated fluorophore

Illustration of exemplary molecule: phospholipid

Figure 2. Illustration of exemplary molecule: Phospholipid

Potential Commercial Applications: Competitive Advantages:
  • Cancer diagnostics
  • Cancer therapeutics
  • Anti-angiogenesis
  • Imaging


Bradford Wood (CC)  ➽ more inventions...

Matthew Dreher (CC)  ➽ more inventions...

Ayele Negussie (CC)  ➽ more inventions...

Intellectual Property:
U.S. Pat: 8,636,978 B2 issued 2014-01-28
PCT Application No. PCT/US2009/047328
US Application No. 13/000,543

W Arap et al. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 1998 Jan 16;279(5349):377-380. PubMed abs
H Ellerby et al. Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med. 1999 Sep;5(9):1032-1038. PubMed abs
F Curnis et al. Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol. 2000 Nov;18(11):1185-1190. PubMed abs
G Colombo et al. Structure-activity relationships of linear and cyclic peptides containing the NGR tumor-homing motif. J Biol Chem. 2002 Dec 6;277(49):47891-47897. PubMed abs
F Pastorino et al. Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. Cancer Res. 2003 Nov 1;63(21):7400-7409. PubMed abs
F Pastorino et al. Targeting liposomal chemotherapy via both tumor cell-specific and tumor vasculature-specific ligands potentiates therapeutic efficacy. Cancer Res. 2006 Oct 15;66(20):10073-10082. PubMed abs
SV Garde et al. Binding and internalization of NGR-peptide-targeted liposomal doxorubicin (TVT-DOX) in CD13-expressing cells and its antitumor effects. Anti-Cancer Drugs. 2007 Nov;18(10):1189-1200. PubMed abs

Licensing Contact:
Edward (Tedd) Fenn, J.D.
Phone: 240-276-6833

OTT Reference No: E-147-2008/0
Updated: Sep 1, 2008