Arlen Myron
North shore univ hosp/hofstra college med and precision biologics, USA
Title: Chemotherapy vs. Specific active immunotherapy in the management of patients with recurrent pancreatic adenocarcinoma
Biography
Biography: Arlen Myron
Abstract
Pancreatic carcinoma in of itself is a relatively lethal malignant disease process. Even when the tumor is small and virtually confined the the pancreatic head where the prognosis is best when compared with body and tail lesions, the overall survival ranges from 5-10 % even following whipple resection. Usually within the short interval of evaluaton of the lesion, nodal and or distant mets is noted with limited survival. Multiple chemotherapeutic forms of intervention have been attempted employing combination drug therapy ie FOLFIERI as well Gemcitabine alone and in combination with Abraxane. These appear offer on average a 3-5 month survival advantage over no intervention. With the discovery of those immunogenic proteins that characterize pancreatic cancer, the opportunity for enhancement in survival using specific active immunotherapy has become a possibility Three oncofetal proteins have now been characterized and represent post translational modifications of mutated MUC5ac, mutated CEAcam5/6 and a mutated form of A33 not previously described. In order to sequence these immunogens for immuno- therapy, monoclonal antibodies were developed for immunopurification , structural identification and sequencing of the antigen. On examination of the antibodies to the target immunogens, it became evident that when immunization was initiated with partially purified protein, the improved survival was a consequence of an ADCC phenomenon and not related to cytotoxic T cell responses to the tumor. The naked MUC5ac antibody, Neo-102 has been used in FDA approved Phase 1/2 studies and is being prepared for Phase III investigation with the monoclonals alone and in combination with chemotherapy. With the ability to radiolabel the antibodies for RT and with the possible addition of checkpoint inhibitors and those lymphokines enhancing the antitumor effects of the mAb the potential of total control of the disease becomes a possibility.