Adjuvant therapy of pancreatic cancer using monoclonal antibodies and immune response modifiers

Pancreatic cancer is a devastating disease with poor survival. At present, no effective adjuvant or palliative therapies are available. Unresponsiveness to chemotherapy, radiotherapy, and antihormonal treatment is one of the reasons that pancreatic cancer patients have an overall median survival time of 4-6 mo. This article summarizes clinical trials on immunotherapy of pancreatic cancer using the murine monoclonal antibodies (MAbs) 17-1A and BW 494. In addition, the use of MAb treatment in combination with immune response modifiers is discussed. In four clinical trials, MAb 17-1A was given by iv infusion to 100 patients with pancreatic cancer. In 30 of these patients, antibody treatment was accompanied by gamma-interferon, also given intravenously. Complete response, partial response, and stable disease were reported in 1, 5, and 23 patients, respectively. Passive immunotherapy using the MAb BW 494 was carried out in 148 pancreatic cancer patients in two phase I and two phase II trials. In 1 out of 75 patients a partial response and in 25 out of 74 patients stable disease were reported. However, in a controlled, randomized trial enrolling 61 patients following Whipple resection, comparable survival times in patients with and without MAb BW 494 treatment led to the termination of further clinical trials with this antibody. New clinical studies using humanized MAbs in combination with immune response modifiers should be initiated to further evaluate immunotherapy as a treatment option in pancreatic cancer.