Pancreatic cancer vaccine: a unique potential therapy

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological checkpoints. Keywords: pancreatic cancer, vaccines, T-cells, antibody, immunotherapy Pancreatic cancerAlthough lung, breast, prostate, and colorectal cancers are considered to be the "big four" cancer types in the USA, pancreas and liver cancers are expected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related deaths by 2030, respectively.1 Pancreatic ductal adenocarcinomas (PDAs) arise from the exocrine pancreas and account for 95% of pancreatic cancers. In the USA, there were an estimated 48,960 cases of new-onset pancreatic cancer in 2015, which led to 40,560 deaths, with a 5-year survival rate of ∼7%.3 PDA is nearly universally lethal; ,20% of patients are suitable candidates for surgery at the time of diagnosis, and the median survival rate is 3.5 months and 12.6 months for nonresected patients and resected patients, respectively.2,4 PDA evolves from noninvasive precursor lesions that do not invade the basement membrane. [5][6][7] Three precursors have been characterized, namely, pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms.