723P - Adoptive immunotherapy with MUC1-specific cytotoxic T lymphocytes and MUC1-mRNA transfected dendritic cells plus gemcitabine for unresectable pancre...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Cancer Immunology and Immunotherapy
Pancreatic Cancer
Presenter Yoshitaro Shindo
Authors Y. Shindo, S. Hazama, Y. Inoue, Y. Maeda, M. Iida, N. Suzuki, K. Yoshimura, T. Ueno, S. Yoshino, M. Oka
  • Department Of Digestive Surgery And Surgical Oncol, Yamaguchi University Graduate School of Medicine, 755-8505 - Ube/JP

Abstract

Background

Prognosis of pancreatic cancer is still poor. Gemcitabine (GEM) is currently considered as a key drug for patients with pancreatic cancer. However, patients treated with GEM alone still have a poor prognosis. To create a more effective therapy, we conducted adoptive immunotherapy with MUC1- Specific cytotoxic T lymphocytes sensitized with a pancreatic cancer, YPK-1, expressing MUC1 (MUC1-CTL) and MUC1-mRNA transfected dendritic cells (MUC1-DC) plus Gemcitabine. The purpose of this study was to evaluate the clinical efficacy of this immunotherapy.

Patients and methods

Between 2007 and 2012, 34 patients with unresectable or recurrent pancreatic cancer histologically confirmed as invasive ductal carcinoma were treated. The median age was 62.5 years, and range 37-81. Peripheral blood mononuclear cells were separated into adherent cells for induction of MUC1-DCs and floating cells for MUC1-CTLs. DCs were generated by culture with granulocyte macrophage colony-stimulating factor and interleukin-4 and then exposed to tumor necrosis factor-α. Matured DCs were transfected MUC1-mRNA by electroporation (MUC1-DCs). MUC1-CTLs were induced by co-culture with YPK-1 and then with interleukin-2 (IL-2). Patients were treated with GEM (1000 mg/m2) for 3 weeks (on days 1, 8, and 15) followed by 1 week of rest, while MUC1-DCs were injected intradermally and MUC1-CTLs were given intravenously on day 18 every 4 weeks. Patients were repeated by received this Adoptive Immunotherapy until progressive disease was recognized.

Results

The median survival time was 9.6 months, and the 1-year survival rate was 43.2%.Of 34 patients, One patient had partial response(2.9%). 19 patients had stable disease(55.9%). The median survival time of the 28 patients who underwent AIT with MUC1-DC over 1x107cells/time was 13.9 months, and the 1-year survival rate of them was 53.8%. Of 29 patients who had no liver metastasis before this treatment, only 4 patients had liver metastasis after treatment. The median survival time of the 29 patients who had no liver metastasis before this therapy was 13.9 months, and the 1-year survival rate of them was 51.2%. No side effects of AIT were observed.

Conclusion

Adoptive Immunotherapy with MUC1- CTL and MUC1-DC plus GEM may be feasible and effective for pancreatic cancer.

Disclosure

All authors have declared no conflicts of interest.