Immunotherapy for Pancreatic Cancer

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  • FUJISAWA TOSHIO
    Department of Gastroenterology, Juntendo University Graduate School of Medicine
  • ISAYAMA HIROYUKI
    Department of Gastroenterology, Juntendo University Graduate School of Medicine

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Abstract

<p>The morbidity rate of pancreatic cancer has increased globally over the last 50 years and it is the most difficult cancer to cure. However, treatments for pancreatic cancer are rapidly advancing. Combination chemotherapy using gemcitabine and nab-paclitaxel (GnP) or fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the standard first-line therapy. However, small molecule agents may cause side-effects, such as myelosuppression. Immunotherapy for cancer has attracted attention and was recognized as the most important scientific advance in 2013 by the journal Science. Immunotherapies include effector cell therapy, treatment via immune checkpoint inhibitors, and cancer vaccines. Currently, only immune checkpoint inhibitors are used for treating pancreatic cancer. Pembrolizumab is an immune checkpoint inhibitor that can be used to treat pancreatic cancer and is indicated for microsatellite instability-high/DNA mismatch repair deficient (MSI-H/dMMR) solid tumors. MSI-H generates neoantigens, the expression of which increases the number of tumor-infiltrating lymphocytes. Through this mechanism, pembrolizumab can significantly improve the clinical condition of patients. However, MSI-H is present in only 2% of pancreatic cancers, such that 98 out of 100 patients receive no benefit from pembrolizumab. IL-13Rα2 is a cancer-testis antigen targeted by the immunotoxin, IL-13 (Pseudomonas exotoxin). A total of 70% of pancreatic cancers strongly express IL-13Rα2, and IL-13PE shows anti-cancer effects in orthotopic mouse models. Clinical trials of IL-13PE, for the treatment of glioblastoma multiforme and adrenocortical carcinoma, are currently being performed. Immunotherapy will likely emerge as the fourth pillar of cancer treatment, along with surgery, chemotherapy, and radiation therapy.</p>

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