Kimura Y.,Tella Inc. |
Tsukada J.,Tella Inc. |
Tsukada J.,Musashino University |
Tomoda T.,Seren Clinic |
And 10 more authors.
Pancreas | Year: 2012
OBJECTIVES: In the current study, we have evaluated the clinical and immunological responses in patients with advanced pancreatic carcinoma who received dendritic cell (DC)-based immunotherapy in combination with gemcitabine and/or S-1. METHODS: Dendritic cell-based immunotherapy (DC vaccine alone or DC vaccine plus lymphokine-activated killer [LAK] cell therapy) in combination with gemcitabine and/or S-1 has been carried out in 49 patients with inoperable pancreatic carcinoma refractory to standard treatment. RESULTS: Of 49 patients, 2 patients had complete remission, 5 had partial remission, and 10 had stable disease. Prolongation of survival in this cohort was highly likely (median survival, 360 days). Survival of patients receiving DC vaccine and chemotherapy plus LAK cell therapy was longer than those receiving DC vaccine in combination with chemotherapy but no LAK cells. Increased numbers of cancer antigen-specific cytotoxic T cells and decreased regulatory T cells were observed in several patients on immunotherapy, but increased overall survival time tended to be associated only with the latter. None of the patients experienced grade 3 or worse adverse events during the treatment period. CONCLUSIONS: Dendritic cell vaccine-based immunotherapy combined with chemotherapy was shown to be safe and possibly effective in patients with advanced pancreatic cancer refractory to standard treatment. Copyright © 2012 by Lippincott Williams & Wilkins.
Kan S.,Jikei University School of Medicine |
Koido S.,Jikei University School of Medicine |
Okamoto M.,Kitasato University |
Hayashi K.,Jikei University School of Medicine |
And 6 more authors.
Oncology Reports | Year: 2015
Trastuzumab emtansine (T-DM1), trastuzumab-conjugated with a cytotoxic agent, has shown promising antitumor effects in breast cancer. Since a good therapeutic response using T-DM1 treatment requires high human epidermal growth factor receptor 2 (HER2) expression, breast cancers with low or no HER2 expression have not been used for T-DM1 treatment. The aim of the present study was to show that treatment of low HER2-expressing breast cancer cells with gemcitabine (GEM) enhanced HER2 expression using RT-qPCR, immunoblot and flow cytometric analysis. The results showed that GEM treatment significantly enhanced HER2 expression in MDA-MB-231, MCF7 and BT-20 breast cancer cells, while paclitaxel (PTX) treatment induced lower or no enhancement in HER2 expression. The expression of HER2 mRNA was also enhanced in GEM-treated MCF7 cells. Treatment with an inhibitor for nuclear factor-(NF)-κB suppressed GEM-induced HER2 upregulation, indicating that NF-κB activation by GEM may be associated with HER2 upregulation. T-DM1 binding to HER2 on MCF-7 cells was enhanced by GEM pretreatment and the combined treatment of GEM and T-DM1 synergistically inhibited the proliferation of MCF7 cells. Thus, the combined treatment with GEM and T-DM1 may be a promising therapeutic modality for low HER2-expressing breast cancers, which was facilitated by the unique HER2-upregulating effect of GEM. © 2015, Spandidos Publications. All rights reserved.
Tella Inc and Kyushu University | Date: 2012-06-20
A technique is needed which can amplify NK cells in vitro and prepare optimum number of NK cells for the adoptive immunotherapy. A method for amplifying NK cells is provided which comprises steps of: preparing cell population which is comprised of NK cells, removing T cells from the cell population which is comprised of NK cells, and, after removal of T cells, cultivating the remaining cells in a medium supplemented with 2500 to 2831 IU/mL of IL-2. The method for amplifying NK cells of the present invention may comprise a step of removing hematopoietic progenitor cells from the cell population. The present invention provides a pharmaceutical composition for adoptive immunotherapy, comprising NK cells which are prepared by the amplifying method of the present invention.
Kyushu University and Tella Inc. | Date: 2014-05-05
The object of the present invention is to develop a technique in which NK cells having a high cytotoxic activity can be prepared with high purity from hematopoietic precursor cells without using a serum or feeder cells of an animal. A method for expanding NK cells includes the steps of expanding hematopoietic precursor cells under a single culturing condition using a medium supplemented with IL-15, SCF, IL-7 and Flt3L, and differentially inducing the cells obtained in the expanding step into NK cells under a culturing condition using a medium supplemented with IL-2. A pharmaceutical composition contains the NK cells prepared by the method for expanding NK cells of the present invention. The pharmaceutical composition of the present invention is used for treating an infectious disease and/or a cancer.
Okamoto M.,Musashino University |
Okamoto M.,Tella Inc. |
Yusa S.,Musashino University |
Yusa S.,Tella Inc. |
And 3 more authors.
Biotherapy | Year: 2010
Dendritic cell (DC)-based immunotherapy in combination with gemcitabine (GEM) and/or S-1 was carried out in 49 patients with inoperable pancreatic cancer refractory to standard treatment. Responses to the therapy (tumor regression, decrease of tumor markers) were observed in 23 of 49 patients. Two patients showed CR, 4PR, 11SD. Prolongation of the survival time was also observed. Increase in the number of WT1 tetramer-positive cells and decrease of regulatory T cells were detected in the patients who showed CR. In the current study, it has been suggested that DC vaccine-based immunotherapy might be effective in the patients with advanced pancreatic cancer refractory to standard treatment. We are now planning to undertake a making the plan of the prospective clinical study using chemo-immunotherapy.