Newer Immunotherapeutic Approaches in Managing Metastatic Pancreatic Cancer

Special Article - Pancreatic Cancer

Austin J Gastroenterol. 2016; 3(2): 1064.

Newer Immunotherapeutic Approaches in Managing Metastatic Pancreatic Cancer

Arlen M¹*, Arlen P³, Coppa G¹, Crawford J¹, Dubukovskiy A², Saric O³, Conte C¹ and Molmenti E¹

¹Division of Surgical Oncology, NorthShore University Health System, USA

²Division of Pathology, NorthShore University Health System, USA

³Precision Biologics, Northwell Health System Hofstra College of Medicine, USA

*Corresponding author: Arlen M, Division of Surgical Oncology, NorthShore University Health System, USA

Received: May 23, 2016; Accepted: August 26, 2016; Published: August 29, 2016


Pancreas Cancer remains one of the more difficult lesions to manage whether at the time of diagnosis or when seen for recurrent disease. When the tumor is operable by one of several surgical procedures depending on site of origin, survival rarely exceeds 10% at the 2 year level post op. When initially diagnosed with a metastatic lesion, survival of the patient rarely reaches 1 year. Chemotherapy becomes the standard method of treatment. When Gemcitabine is utilized the survival is found to be in the range of 5 months and when this is followed by Abraxane, an additional 7-10 wks can be expected.

In order to improve survival beyond that achieved by chemotherapy alone, immunotherapeutic agents are being introduced, with the hope of enhancing the overall survival rate. Many immunogenic targets have been defined, but those offering the best opportunity for accomplishing the needed response are proteins (TAA’s) expressed by the tumor that are immunogenic and specifically characterize that lesion without cross reactivity to normal tissue.

We have found in our studies of colorectal carcinoma that several tumor associated antigens are present and that one in particular, the post translational modification of MUC5ac is highly expressed in many cases of pancreatic cancer. This protein is present mainly tumors of the colon and pancreas but at levels too low to be recognized by the host immune system. After isolating this TAA and measuring levels of its expression by the tumor, few lesions contain more than 25-50 ugms. A detailed study of levels necessary to induce the proper immune response has been shown to be between 500 and 1000 ugms. We have also looked at mechanisms by which TAA, when delivered at proper levels produce immune suppression of the lesion. The mechanism has been shown to primarily be IgG1 expression by the B cells and that the cytotoxic T cells do not play a major role. The monoclonals do not directly affect the tumor by rather function through ADCC (antibody dependent cell cytotoxicity). In the present paper discussing our clinical trials, patients entered have failed all therapeutic approaches, have been shown to express the proper target antigen and as such receive 400 mg. antibody IV q 2 wks. The nature of the tumor antigen, development of the monoclonal system employed and status of the ongoing FDA trial is described.

Keywords: Pancreatic cancer; Tumor; Patients


Among the various solid tumor malignancies, one of the more aggressive lesions, one that exhibits a high mortality rate virtually from its earliest stages of inception is the pancreatic adenocarcinoma [1]. This is based on the fact that among those primary lesions to be encountered and evaluated during early stages of development, that metastasis will probably be detected in most of the patients [2]. Survival, for such lesions is for the most part based on progression of disease seen months after diagnosis rather than the longer periods seen with other GI malignancies. The end stage for this form of cancer occurs rapidly even though numerous therapeutic approaches have been applied to control the primary lesion and any existing metastatic growths. Should one detect the primary early enough in its clinical onset, so that resection of tumor is feasible, at the end of a two year period post surgery, roughly 10% of patients will have survived [3]. As such diagnosis usually is achieved late in the clinical course of disease.

Early recognition of tumor presence is usually not accomplished in spite of detecting minor complaints with minimal symptoms related to the appearance of the pancreatic cancer. At the present time the use of blood tests defining serum markers specific for pancreatic cancer are not that effective [4,5,6].

Should one examine the histologic findings that define the early onset of this disease, it will be noted that the initial transformation to malignancy arises within the ductal mucosa of the pancreas in a pattern similar to what is seen with ductal carcinoma in situ (DCIS) of the breast [7] (Figure 1). The genetic alterations occurring within the mucosal cell occurs over a 15-20 year period of time until the insitu premalignant cells show signs of ductal invasion to then present as an early lesion within pancreatic parenchyma [8].