Blockade of Surface Alpha-Enolase (ENO1) as a Novel Immunotherapeutic Approach in Pancreatic Cancer

Moitza Principe,Paola Cappello

doi:10.4172/2167-7700.1000188

Abstract

In 2010 in Italy, there were 175,046 cancer deaths, with total mortality rates, respectively for men and women, of 138 and 83/100,000 [1]. Total cancer mortality in Italy has been declining since the 1980s in men and earlier in women [1], similarly to most European countries [2] and the United States [3]. However, some rising trends have also been observed, notably for female lung cancer and pancreatic cancer in both sexes [1]. Although the incidence of pancreatic cancer is relative low compared to other tumor types such as breast, lung and prostate cancer, in pancreatic cancer the mortality is almost equal to the incidence level, with 41,780 and 40,560 deaths predicted in Europe and USA respectively [2,4]. For this reason, PDA is the 4th leading cause of cancer deaths in the Western Countries [1,2,4]. Despite the efforts of clinicians and scientists, pancreatic cancer has the worst prognosis of all major malignancies, with a 5-year survival rate of 8% [4].

Highlights

In 2010 in Italy, there were 175,046 cancer deaths, with total mortality rates, respectively for men and women, of 138 and 83/100,000 [1]
In recent years, targeted therapies have been tested for treating metastatic pancreatic cancer, for example Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) (ClinicalTrials.gov number NCT01608841), is a successful example of how using an antibody, in combination with gemcitabine-based chemotherapy, is effective in improving overall and progression-free survival, as well as response rates in metastatic Pancreatic ductal adenocarcinomas (PDA) patients [6]
After injection of the Associated Viral Vector (AAVV) expressing anti-ENO1 monoclonal antibody (mAb) (Figure 1 left panel), the presence of the mAb in the mouse sera progressively increased from 1 to 4 weeks after injection. This continuous, long-lasting and sustained production of circulating antiENO1 mAb resulted in the observation of a significant decrease in lung metastases compared to control mice, producing a more pronounced effect compared to biweekly inoculation of anti-ENO1 mAb (Figure 1 left panel)[13]. These findings strongly suggest that blocking the ENO1/plasminogen interaction through the injection of AAVV-antiENO1 mAb could provide a new therapeutic approach for treating metastatic PDA patients

Summary

Introduction

In 2010 in Italy, there were 175,046 cancer deaths, with total mortality rates, respectively for men and women, of 138 and 83/100,000 [1]. In recent years, targeted therapies have been tested for treating metastatic pancreatic cancer, for example Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) (ClinicalTrials.gov number NCT01608841), is a successful example of how using an antibody, in combination with gemcitabine-based chemotherapy, is effective in improving overall and progression-free survival, as well as response rates in metastatic PDA patients [6]. ENO1 is a multi-functional protein, acting as both a glycolytic enzyme and a plasminogen receptor expressed on the cell surface of tumor cells, playing a critical role in metastasis and spreading [9].

Results

Conclusion