NOVEL%20PROGNOSTIC%20AND%20IMMUNOTHERAPEUTIC%20APPROACHES%20TO%20PATIENTS%20WITH%20SOLID%20TUMORS

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:

NY-ESO-1 mol/β β -actin mol

1) In vitro and in vivo immunomodulatory and immunotherapeutic potential of novel DNA hypomethylating agents; 1,2E-03 9,0E-04 6,0E-04 3,0E-04 0,0E+00 5

2) DNA methylation as prognostic predictive marker of disease outcome in solid tumors;

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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;

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IL-2 (5x105 I.U./12h) OR GM-CSF (4x105 I.U./12h)

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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