Researchers have developed a novel, bacterial-based immunotherapy that homes to tumors and initiates an effective tumor-killing response.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth-leading cause of cancer death, with an average survival time of less than one year after diagnosis. Its high morbidity stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. Compared to other cancers, PDAC demonstrates marked resistance to conventional forms of chemotherapy, which does not increase survival by more than a few months. Earlier detection and targeted therapies are necessary to improve the prognosis of PDAC patients.
One promising and effective strategy uses genetically modified, non-pathogenic bacterial species as vehicles for delivery of therapeutic agents to tumors. Studies have shown that certain species of anaerobic bacteria are able to colonize and thrive in necrotic regions of tumors, as compared to more oxygenated regions. Because of their selectivity for tumor tissues with limited toxicity to normal tissues, these bacteria would be ideal vectors for cancer therapies.
Recently, City of Hope researchers reported a novel immunotherapy that resulted in complete regression of pancreatic tumors and significantly extended survival in mouse studies . The group engineered an attenuated form of Salmonella typhimurium carrying a small hairpin RNA against indoleamine 2,3-dioxygenase (IDO), a potent, immunosuppressive molecule that essentially helps cancer cells evade the immune system. They tested the efficacy of this modified bacteria, shIDO-ST, in combination with PEGPH20, an enzyme that digests hyaluronic acid, a component of PDAC stroma that forms a physical barrier to drug delivery. The combinational therapy resulted in tumor regression in the majority of mice, with no evidence of tumors 2 weeks after treatment and up to 8 weeks after tumor implantation. Interestingly, the authors observed significant colonization of the tumors by shIDO-ST only with PEGPH20 pretreatment, suggesting that PEGPH20 does indeed promote permeability within otherwise impermeable PDAC tumors.
Taken together, their results suggest that simultaneously targeting the permeability of tumor stroma and immunosuppression significantly enhance antitumor responses, providing an effective treatment for PDAC. HemaCare looks forward to translation of this novel cancer immunotherapy into the clinic, and provides a wide array of cancer disease-state blood products and primary cells for research purposes.
 Manuel, E. R. et al. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors. Cancer immunology research, doi:10.1158/2326-6066.cir-14-0214 (2015).