Centre National De La Recherche Scientifique

Korea Institute of Science and Technology

Institut National De La Sante Et De La Recherche Medicale

Universite Claude Bernard – Lyon1

Centre Leon Berard

Kist Corp.

Inserm

Philippe Bertolino

Ana Hennino

Kim In-San

The present invention relates to a non invasive diagnostic method of pancreatic ductal adenocarcinoma (PDAC) in a subject said method comprising the step of measuring the level of βig-h3 protein in a blood sample wherein the serum level of βig-h3 is positively correlated with the risk of having a PDAC. By following studies on 2 distinct cohorts of 20 and 104 of PDAC patients, and on PDAC mouse model, the inventors show that βig-h3 can be directly detected in the blood sample and βig-h3 is expressed very early in tumorigenesis in pancreatic neoplastic lesions. The present invention also relates to antagonist of βig-h3 protein, for use in the treatment of PDAC. The inventors found that βig-h3 bind directly on CD8T cells by reducing their activation and cytotoxic properties. Furthermore, the use of neutralizing βig-h3 antibodies in PDAC mouse model, reduced tumor growth by enhancing CD8T cell anti-tumoral response. Thus, neutralizing βig-h3 which acts as a novel immunological check-point target in PDAC therefore allows to restore beneficial anti-tumor immunity in PDAC.

Early and non invasive method for assessing a subject's risk of having pancreatic ductal adenocarcinoma and methods of treatment of such disease

A non invasive diagnostic method of pancreatic ductal adenocarcinoma (PDAC) in a subject is provided. The method comprises the step of measuring the level of &#x3b2;ig-h3 protein in a blood sample wherein the serum level of &#x3b2;ig-h3 is positively correlated with the risk of having a PDAC. By following studies on 2 distinct cohorts of 20 and 104 of PDAC patients, and on PDAC mouse model, the inventors show that &#x3b2;ig-h3 can be directly detected in the blood sample and &#x3b2;ig-h3 is expressed very early in tumorigenesis in pancreatic neoplastic lesions. Also provided is a &#x3b2;ig-h3 protein, for use in the treatment of PDAC. The inventors found that &#x3b2;ig-h3 bind directly on CD8T cells by reducing their activation and cytotoxic properties. Furthermore, the use of neutralizing &#x3b2;ig-h3 antibodies in PDAC mouse model reduced tumor growth by enhancing CD8T cell anti-tumoral response. Thus, neutralizing &#x3b2;ig-h3 which acts as a novel immunological check-point target in PDAC therefore allows to restore beneficial anti-tumor immunity in PDAC.

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Lyons, France

Philippe Bertolino