Immunotherapy with monoclonal antibody (Mab) in pancreatic adenocarcinoma.
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.
Tempero
M A
MA
University of Nebraska Medical Center, Omaha.
Haga
Y
Y
Sivinski
C
C
Steplewski
Z
Z
Kay
H D
HD
Pour
P
P
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D007371:Interferon-gamma