Brief Introduction

The Research activities of Flavio Curnis, performed in tight collaboration with the other components of the Angelo Corti’s group, have been focused on studies aimed at developing new strategies to increase the therapeutic index of anti-tumor cytokines such as TNF, IFN, and IL12 by targeting them to the tumor vasculature, using, as vehicles, tumor vasculature-homing peptides. F. Curnis has significantly contributed to the development of NGR-TNF, an NGR peptide-cytokine fusion derivative, that has been studied in a broad clinical program in cancer patients alone and in combination with chemotherapy or immunotherapy (19 clinical trials, >1000 treated patients, including one phase II trial in primary CNS lymphoma). He has also contributed to the discovery the isoDGR motif, a novel integrin-binding motif, and demonstrated that isoDGR containing peptides can be exploited as ligands for targeted delivery of cytokines, fluorescent and radioactive compounds to αvβ3-positive tumor vessels. In addition, he has recently demonstrated that NGR- or isoDGR-tagged nanogold provides a versatile platform for the delivery of single or multiple cytokines to tumor vessels to increase vascular permeability, enhance drug penetration, and immune cell infiltration. The fact that NGR-TNF has reached phase II-III clinical studies documents his ability to conduct basic and translational research studies on the delivery of cytokines to tumors aimed at altering the barriers that limit drug penetration and immune cell infiltration into tumor tissue.

Research Activity 

Flavio Curnis, currently, is the PI of a project focused on glioblastoma (GBM), the most frequent and aggressive brain tumor. All clinical trials on this disease have failed, mostly because of the limited penetration of the drugs through the blood-brain barrier (BBB) and their poor distribution in the heterogeneous GBM tissue.  The project hypothesis is that the combination of BBB opening with SNGR-TNF (a more stable derivative of the NGR-TNF validated in brain lymphomas) can improve the treatment of GBM patients. To prove this thesis, SNGR-TNF is being tested in clinically relevant animal models in combination with temozolomide or with nanoparticles loaded with highly active anti-GBM drugs and functionalized with specific peptides that may improve tumor penetration and access to cancer cells. 

Another relevant research activity carried out by Flavio Curnis in collaboration with the other components of the Angelo Cortis’s group are related to the development and use of a chromogranin A derived peptide capable of recognizing the alphav/beta6 and alphavbeta8, two integrins that are overexpressed by various solid tumors, and which have a role in TGFbeta maturation (an important immunosuppressive mechanism in tumors).