CENTRO DI RIFERIMENTO ONCOLOGICO

Technology Transfer Opportunities

Contact: Ermes Mestroni emestroni@cro.it

NOVEL PROGNOSTIC AND IMMUNOTHERAPEUTIC

APPROACHES TO PATIENTS WITH SOLID TUMORS

Technology overview

The Advanced Immunotherapy Unit of CRO has a long-standing tradition in translational

clinical research focused on the laboratory development and clinical application of novel

immunotherapeutic agents for the treatment of cancer patients. Among ongoing research

activities, a specific interest focuses on epigenetic alterations of neoplastic cells, which are

pharmacologically-reversible DNA modifications occurring in cancer.

More specifically, DNA methylation is being investigated as a tool to design new

therapeutic strategies and to identify novel molecular prognostic and predictive markers in

patients with solid tumors. Main research themes, which are developed in tight

collaboration with the Division of Medical Oncology and Immunotherapy of the Azienda

Ospedaliera Universitaria of Siena (AOUS), Italy, are:

1) In vitro and in vivo immunomodulatory

and immunotherapeutic potential of

novel DNA hypomethylating agents;

0,0E+00

3,0E-04

6,0E-04

9,0E-04

1,2E-03

5 10 20 30

NY-ESO-1 mol/ββ ββ-actin mol

2) DNA methylation as prognostic

predictive marker of disease outcome in

solid tumors;

CENTRO DI RIFERIMENTO ONCOLOGICO

Technology Transfer Opportunities

Contact: Ermes Mestroni emestroni@cro.it

3) Anti-idiotypic monoclonal antibodies

for vaccination of cancer patients with

High Molecular Weight-Melanoma

Associated Antigen-positive tumors;

Weeks of treatment

�Id 2 mg i.d.

IL-2

(5x105 I.U./12h)

0 1 4 8

GM-CSF (4x105 I.U./12h)

OR

4) Endoglin/CD105, a marker of tumor

angiogenesis, for diagnostic and

therapeutic applications in solid tumors.

Advantages

1) Our work has demonstrated that epigenetic drugs bear a previously unknown immunomodulatory and immunotherapeutic potential in human tumors of different

histotype;

2) We have generated evidences that DNA methylation represents a molecular prognostic marker of clinical outcome in cutaneous melanoma;

3) We have shown the clinical and immunomodulatory potential of anti-idiotypic mouse antibody vaccines in melanoma patients;

4) We have developed and characterized a mouse monoclonal antibody reactive to endoglin/CD105. In vitro and in vivo studies demonstrated that this agent quantitates

tumor-associated microvasculature, images tumors in vivo, and that it is a candidate

anti-angiogenic therapeutic agent.

Research activities have attracted founding from national and international agencies, as

well as from pharmaceutical companies, including: AIRC (Maio and Sigalotti),

Fondazione Monte dei Paschi di Siena (Coral), the Harry J Lloyd Charitable Trust, KS,

USA (Maio), ISS (Maio), Italian Ministry of Health (Maio), Bristol Myers Squibb

(Maio), Pfizer Inc., NY, USA (Maio), SuperGen, Inc., CA, USA (Maio).

CENTRO DI RIFERIMENTO ONCOLOGICO

Technology Transfer Opportunities

Contact: Ermes Mestroni emestroni@cro.it

Development stage

1) The characterization of the in vitro and in vivo immunomodulatory and immunotherapeutic activities of new DNA hypomethylating drugs is being developed;

2) A joint european patent application between CRO and the Azienda Ospedaliera Universitaria of Siena has been submitted on the prognostic and predictive role of DNA

methylation in melanoma (inventors Maio and Sigalotti);

3) A phase II clinical trial has been completed with an anti-idiotypic mouse monoclonal antibody;

4) The anti-angiogenic activity of our anti-endoglin/CD105 mouse monoclonal antibody is being compared to that of other anti-endoglin/CD105 therapeutic antibodies in early

stages of clinical development.

Looking for

⇒ Industrial partners interested in the laboratory and clinical development of our

technologies and products.

More Information

Dr. Michele Maio

Advanced Immunotherapy Unit

mmaio@cro.it

Phone: +39-0434-659342

Dr. Luca Sigalotti / Dr. Sandra Coral

Advanced Immunotherapy Unit

lsigalotti@cro.it

scoral@cro.it

Phone: +39-0434-659569