BBB Seminar: Dominique Lombardo
Immunotherapy of pancreatic cancer
Dominique Lombardo, French National Institute of Health and Medical Research (INSERM), Marseille, France
Pancreatic adenocarcinoma (PDAC) is among the group of extremely aggressive neoplastic diseases and remains one of the most resistant cancers to current therapies, killing more than 266 000 patients worldwide per year (2008). Its curative resection rate is very low due to unspecific symptoms, the lack of early specific biological markers, delayed diagnosis and metastases formation. Up to 80% of patients presented with advanced or metastatic disease have a median survival ranging from 6 to 9 months. For these patients with advanced or metastatic cancer, the main treatment is a combination of chemotherapy and radiation therapy or chemotherapy alone in unfit patients. At this stage, most of these therapeutic strategies, based on current protocols, are ineffective. Noteworthy, antibodies to ubiquitous growth factor receptors also fail in treating PDAC. Identifying and validating sensitive and specific biological markers, is a pre-requisite to propose new therapeutic approaches. These markers would be useful to target neoplastic pancreatic cells by new chemotherapies and/or passive immunotherapies. Therefore novel targets/protocols are urgently needed for the improvement of PDAC treatment. We have developed and evaluated the efficiency of a proprietary monoclonal antibody (mAb16D10) directed against a glyco-variant of the bile salt-dependent lipase, a pancreatic enzyme involved in lipid digestion in normal humans. This mAb, which binds to related blood group A glycan structures, specifically targets pancreatic cancer cells from patients of B and O blood groups. MAb 16D10 does not bind to human normal tissues and recognizes selectively pancreatic cancer cells. MAb16D10 induces cancer cell death via cell cycle arrest through induction of pro-apoptotic Bax and p53 proteins. Humanization of the antibody is going on to propose new strategies to reverse the dramatic prognosis of PDAC.
Chair: Pål Rasmus Njølstad, Department of Clinical Medicine