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Immunotherapy with monoclonal antibody (Mab) in pancreatic adenocarcinoma
M A Tempero1, Y Haga, C Sivinski
1University of Nebraska Medical Center, Omaha.
Abstract:
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.
Insights
Monoclonal antibody 17-1A showed limited efficacy in pancreatic cancer trials. Combining it with interferon yielded some stable disease, but further trials with IL-2 were not recommended.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Pancreatic exocrine cancer has a poor prognosis with limited conventional treatment options.
- Novel therapeutic strategies are urgently needed for unresectable pancreatic cancer.
Purpose of the Study:
- To evaluate the efficacy and safety of monoclonal antibody (Mab) 17-1A in patients with unresectable pancreatic exocrine cancer.
- To explore combination therapies involving Mab 17-1A and other immunomodulatory agents.
Main Methods:
- Clinical trials were conducted using Mab 17-1A alone, in combination with autologous mononuclear cells, and with recombinant gamma interferon.
- In vitro studies assessed the effect of Mab 17-1A and IL-2 on pancreatic adenocarcinoma cell lines and effector cell activity.
Main Results:
- Mab 17-1A alone showed no antitumor response and induced antimouse antibody response in 81% of patients.
- Combination therapy with interferon resulted in one complete response and stable disease in six patients.
- High-dose Mab 17-1A caused anaphylaxis; in vitro studies showed no rationale for IL-2 combination therapy.
Conclusions:
- Monoclonal antibody 17-1A has limited efficacy as a monotherapy for pancreatic cancer.
- Combination with interferon showed some benefit, but further development with IL-2 is not supported.
- Future strategies may involve active immunotherapy or targeted toxicity using radioimmunoconjugates like 125I-labeled chimeric Mab 17-1A.