Conventional
therapy of pancreatic exocrine
cancer is disappointing. The poor prognosis of the disease challenges development of novel therapeutic strategies. We report the results of clinical trials of the
monoclonal antibody (
Mab) 17-1A in patients with histologically verified unresectable pancreatic exocrine
cancer. No antitumor response was seen in 18 patients treated with
Mab 17-1A (500 mg) admixed with 10(9) autologous mononuclear cells, and 81% of the patients developed antimouse antibody response. Combination of recombinant
gamma interferon and
Mab 17-1A mixed with autologous mononuclear white cells resulted in complete response of 4-mo duration in 1 out of 25 evaluable patients and unusually stable disease from 4 to 48+ mo in another 6 patients. High intermittent doses of infused
Mab 17-1A did not show any objective antitumor response and caused serious
anaphylaxis in two of the patients in the trial. Because examination of six pancreatic
adenocarcinoma cell lines with different doses of
Mab 17-1A and
IL-2 failed to augment lytic activity of mononuclear effector cells against all
cancer cell lines tested, there seemed to be no rationale for pursuing clinical studies with
IL-2 and
Mab 17-1A in either the murine or chimeric form. Attractive therapeutic approaches include active immunotherapy with immunization using idiotypic
antibodies or targeted toxicity with the use of
radioimmunoconjugates, particularly 125I-labeled chimeric
Mab 17-1A.