Pancreatic cancer is a """"""""rare"""""""" and fata l disease, with few treatment options. Currently, promising antitumor strategies utilize combination therapies, with each agent targeting separate aspects of oncogenesis. Disappointingly, combination of anti- EGFR monoclonal antibody (MAb), cetuximab, with standard-of-care, gemcitabine, failed to improve survival in this disease. Although EGFR is over-expressed in >90% of pancreatic carcinomas -90% also contain KRAS mutations. We herein propose a strategy that could overcome resistance of KRAS mutations to anti-EGFR MAbs. Biothera is developing Imprime-PGG?, a beta 1,3/1,6 glucose polymer, as an adjunct to MAbs for cancer treatment. The proprietary agent, Imprime, induces neutrophil-mediated cellular cytotoxicity, where Imprime 'primes'neutrophils (comprise -50%-70% of human immune cells) to recognize and kill MAb targeted tumors. Preclinically, Imprime has shown therapeutic efficacy as an adjunct to MAbs in various tumor models, including KRAS-mutated lung and colon carcinoma models. This coupled wi th the safety and recent efficacy data from a Phase 1 b/2 metastatic CRC study supports Imprime to be a safe and effective drug. Overall objective is to establish preclinical proof of concept for this novel treatment approach in pancreatic cancer xenografts;both KRAS-wild type and KRASmutant tumors will be studied, and subsequently evaluate therapeutic potential in the clinic.
