Nell`ambito dell`Istituto di Ricerca Urologica, il gruppo è focalizzato

As part of the Research Institute Urology, the group is focused on developing specific approaches
based on toxins delivery for the treatment of bladder cancer. The employment of plant and bacterial
toxins as effectors in cancer therapy has been evaluated in pilot pre-clinical and clinical studies with
promising results. Ribosome-inactivating proteins of plant origin such as SAP are potent protein
synthesis inhibitors, promptly inducing apoptosis of target cells and SAP-based conjugates showed
selective killing of tumor cells. We are developing different systems for SAP delivery and tumor
targeting, improved by the parallel study of the molecular mechanisms underlying tumor occurrence
and progression in order to further identify specific tumor markers as potential therapeutic targets.
Riccardo Vago - Curriculum vitae
Education
2004
2000
Professional Experiences
2014-today
2011-today
2013-2014
2008-2013
2005-2007
2002-2004
2001-2002
2000-2001
2000
1998-2000
PhD in Genetic and Biomolecular Sciences, Università degli Studi di
Milano
Degree in Pharmaceutical Chemistry and Technology, Università
degli Studi di Milano
Group leader, Urological Research Institute, Division of Molecular
Oncology, San Raffaele Scientific Institute, Milan
Lecturer of Biochemistry, Università Vita e Salute San Raffaele,
Milan
Project leader, Department of Biotechnology and Biosciences,
Università degli Studi di Milano-Bicocca
Project leader, Neurogenomics Unit (former Human Molecular
Genetics Unit), San Raffaele Scientific Institute, Milan
Postdoc, Institute of Molecular Genetics - National Research Council,
Pavia
PhD student, Institute for Research in Biomedicine, Bellinzona,
Switzerland
PhD student, Protein Transport and Secretion Unit, San Raffaele
Scientific Institute, Milan
Post-Graduate fellow, Biotechnology Unit, San Raffaele Scientific
Institute, Milan
Visiting fellow, Southampton General Hospital, United Kingdom
Doctoral student, Biotechnology Unit, San Raffaele Scientific
Institute, Milan
Research activities (updated 2014)
Development of toxin-based targeted therapy for the treatment of bladder cancer
Bladder cancer is among the most common and expensive to manage cancers in developed
countries due to a need for continuous monitoring and recurrence treatment. Despite research
efforts, available therapeutic options in bladder cancer have still limited results and alternative
and/or complementary strategies to state-of-art therapies are needed to limit the recurrence and
improve survival. Although extensive molecular characterization of urothelial bladder carcinoma
showed a plethora of alteration in a relevant number of tumors, so far no molecularly targeted
agents have been approved for treatment of the disease.
Plant and bacterial toxins have been increasingly studied as effectors in cancer treatment and some
of them have been used with promising results in pilot preclinical and clinical studies. Ribosomeinactivating proteins such as saporin (SAP) are potent protein synthesis inhibitors, promptly
inducing apoptosis of target cells. In particular, SAP has high enzymatic activity, stability and
resistance to conjugation procedures and blood proteases, thus lending itself well to be used in
cancer therapy. SAP-based conjugates showed selective killing in vitro and in vivo, with only mild
and transient side effects.
We have developed saporin-based chimeric fusions targeted against specific molecules overexpressed on the surface of cancer cells and demonstrated their activity and efficacy in vitro. Our
research activity is based on the employment of such fusions in the treatment of bladder cancer and
on the study of additional molecules as therapeutic targets to be tested in various cellular and animal
models available at the Urological Research Institute. Moreover, it is of our interest to develop
alternative systems for toxin delivery to the tumor to be synergistically used with other treatments.
Analysis of factors leading to bladder cancer occurrence and progression
Tumors depend on a cross talk with the surroundings to guarantee their survival (angiogenesis,
immune escape), to support phenotypic changes (epithelial-to-mesenchymal transition) required to
leave the primary tumor mass and to prepare the bone marrow and pre-metastatic organs allowing
migrating tumor cells to settle and grow. Specific microvesicles termed exosomes are emerging as
important vehicles for tumor-derived factors to modulate pre-metastatic sites, promote neoangiogenesis and reduce immune surveillance.
Most newly diagnosed bladder cancer (around 75%) are non-muscle invasive; nevertheless, a
significant percentage, ranging from 10 to 20%, of low grade superficial tumors progress to highgrade carcinomas, that are initially treated with trans urethral resection of the lesion followed by
chemo- or immunotherapy. Unfortunately, chemo-resistance and side effects often limit the
therapeutic efficacy and the tumors frequently recur and to some extent progress. The muscleinvasive tumors are generally treated by radical cystectomy followed by chemotherapy, but up to
50% of patients develop metastatic disease with a poor prognosis.
The activity of the research group is focused on the study of the mechanisms leading to the
development and progression of bladder cancer, such as stromal reorganization, neo-angiogenesis
and cell migration through the analysis of selected bioactive molecules such as enzymes and RNAs
carried by tumor exosomes. A thorough dissection of the molecular and cellular pathways involved
in these processes is the basis of the identification of possible therapeutic targets.
Selected publications
Vago R, Ippoliti R, Fabbrini MS (2013) “Current status & Biomedical applications of Ribosomeinactivating proteins”. Antitumor Potential and other Emerging Medicinal Properties of Natural
Compounds. Springer
Giansanti F, Giordani V, Vago R, Flavell DJ, Flavell SU, Fabbrini MS, Ippoliti R. (2013)
“Dissecting the entry route of saporin-based anti-CD7 immunotoxins in human T-cell acute
lymphoblastic leukaemia cells” Antibodies 2(1), 50-65
Zarovni N, Vago R, Fabbrini MS. (2009) “Saporin suicide gene therapy” Methods Mol Biol.
542:261-83.
Zarovni N., Vago R., Soldà T., Monaco L., Fabbrini M.S. (2007) “Saporin as a novel suicide gene
in cancer gene therapy” Cancer Gene Ther. 14(2):165-73.
Vago R., Marsden C.J., Lord J.M., Ippoliti R., Flavell D.J., Flavell S.U., Ceriotti A. and Fabbrini
M.S. (2005). “Saporin and ricin, two ribosome-inactivating proteins from plants, differ in their
routes of entry into mammalian cells” FEBS J. 272(19):4983-95