Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer

作者：Shindo Yoshitaro; Hazama Shoichi; Maeda Yoshinari; Matsui Hiroto; Iida Michihisa; Suzuki Nobuaki; Yoshimura Kiyoshi; Ueno Tomio; Yoshino Shigefumi; Sakai Kohei; Suehiro Yutaka; Yamasaki Takahiro; Hinoda Yuji; Oka Masaaki^*

来源：Journal of Translational Medicine, 2014, 12(1): 175.

DOI：10.1186/1479-5876-12-175

• Pancreatic cancer
• MUC1
• Dendritic cell
• Cytotoxic lymphocyte
• Gemcitabine
• Immunotherapy

Background: We previously reported the clinical efficacy of adoptive immunotherapy (AIT) with dendritic cells (DCs) pulsed with mucin 1 (MUC1) peptide and cytotoxic T lymphocytes (CTLs). We also reported that gemcitabine (GEM) enhances anti-tumor immunity by suppressing regulatory T cells. Therefore, in the present study, we performed combination therapy with AIT and GEM for patients with unresectable or recurrent pancreatic cancer. %26lt;br%26gt;Patients and methods: Forty-two patients with unresectable or recurrent pancreatic cancer were treated. DCs were generated by culture with granulocyte macrophage colony-stimulating factor and interleukin-4 and then exposed to tumor necrosis factor alpha. Mature DCs were transfected with MUC1-mRNA by electroporation (MUC1-DCs). MUC1-CTLs were induced by co-culture with YPK-1, a human pancreatic cancer cell line, and then with interleukin-2. Patients were treated with GEM, while MUC1-DCs were intradermally injected, and MUC1-CTLs were intravenously administered. %26lt;br%26gt;Results: Median survival time (MST) was 13.9 months, and the 1-year survival rate was 51.1%. Of 42 patients, one patient had complete response (2.4%), three patients had partial response (7.1%) and 22 patients had stable disease (52.4%). The disease control ratio was 61.9%. The MST and 1-year survival rate of 35 patients who received more than 1 x 10(7) MUC1-DCs per injection was 16.1 months and 60.3%, respectively. Liver metastasis occurred in only 5 patients among 35 patients without liver metastasis before treatment. There were no severe toxicities associated with AIT. %26lt;br%26gt;Conclusion: AIT with MUC1-DCs and MUC1-CTLs plus GEM may be a feasible and effective treatment for pancreatic cancer.

• 出版日期2014-6-19