Tella, Japan
Tella, Japan

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[Problem] To provide a polypeptide which enables stimulation of numerous T cells of different derivation, and to induce strong immunological response against numerous types of cancers. [Solution] Provided is a fused polypeptide that includes a helper epitope derived from the WT1 protein, and a killer epitope derived from the WT1 protein, wherein the polypeptide includes a total of 3 to 6 of the helper epitopes and the killer epitopes per molecule of the fused polypeptide.


Kobayashi M.,Seren Clinic Nagoya | Shimodaira S.,Shinshu University | Nagai K.,Nagasaki University | Ogasawara M.,Sapporo Hokuyu Hospital | And 12 more authors.
Cancer Immunology, Immunotherapy | Year: 2014

Objective: Dendritic cell (DC)-based cancer vaccines may have a significant benefit to patients with advanced pancreatic cancer. However, variations among clinical studies make it difficult to compare clinical outcomes. Here, we identified factors that determined the clinical benefits by analyzing data obtained at seven Japanese institutions that employed the same DC preparation and treatment regimens. Methods: Of 354 patients who met the inclusion criteria, 255 patients who received standard chemotherapy combined with peptide-pulsed DC vaccines were analyzed. Results: The mean survival time from diagnosis was 16.5 months (95 % CI 14.4-18.5) and that from the first vaccination was 9.9 months (95 % CI 8.0-12.9). Known prognostic baseline factors related to advanced pancreatic cancer, namely ECOG-PS, peritoneal metastasis, liver metastasis, and the prognostic nutrition index, were also representative. Importantly, we found that erythema reaction after vaccination was an independent and treatment-related prognostic factor for better survival and that OK-432 might be a good adjuvant enhancing the antitumor immunity during DC vaccination. Conclusions: This is the first report of a multicenter clinical study suggesting the feasibility and possible clinical benefit of an add-on DC vaccine in patients with advanced pancreatic cancer who are undergoing chemotherapy. These findings need to be addressed in well-controlled prospective randomized trials. © 2014 Springer-Verlag.


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.


PubMed | AllGene Inc., Tella Inc., Kyushu University and Kanamecho Hospital
Type: | Journal: SpringerPlus | Year: 2015

For the production of tumor-specific vaccines, including dendritic cell (DC) vaccines, the tumor cells themselves are an ideal source. Floating tumor cells in the ascites fluid from patients with malignant ascites are a good candidate source, but it is not easy to obtain pure tumor cells from ascites because of various types of cell contamination as well as protein aggregates. We here report an effective method to recover pure tumor cells from malignant ascites. We used lavage fluid from 13 patients with malignant ascites who were treated with modified cell-free and concentrated ascites reinfusion therapy (KM-CART). Cellular components were separated from the lavage fluid by centrifugation, enzymatic digestion and hemolysis. Tumor cells were purified by depleting CD45(+) leukocytes with antibody-conjugated magnetic beads. The tumor cell lysate was extracted by freeze-and-thaw cycles. The mean obtained total cell number was 7.5010(7) cells (range 4.4010(6)-2.4810(8) cells). From this fraction, 6.3910(6) (range 3.2310(5)-2.5310(7)) CD45(-) cells were collected, and the tumor cell purity was over 80% defined as CD45(-)CD326(+). A sufficient amount of tumor lysate, average=2416g (range 25-8743g), was extracted from CD45(-)CD326(+) tumor cells. We here established an effective method to produce highly purified tumor cells from KM-CART lavage fluid. The clinical feasibility of this simple preparation method for generating tumor lysate should be examined in clinical studies of DC vaccines.


Patent
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.


Patent
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.


Patent
Kyushu University and Tella Inc. | Date: 2014-04-30

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.


Patent
Kyushu University and Tella Inc. | Date: 2016-03-30

[Problem to be Solved] 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. [Solution] 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.


The object aims to provide: a novel tumor antigen; a novel therapeutic agent useful in a method for treating a malignant neoplasm by utilizing the tumor antigen; and a tumor antigen which can be used as the therapeutic agent. Thus, disclosed are: a novel tumor antigen which has an epitope capable of inducing a Th1 cell which is a CD4-positive T cell specific to Survivin; and use of the tumor antigen. Specifically disclosed is a polypeptide which comprises an amino acid sequence depicted in SEQ ID NO:17 or the like and has an activity to cause the production of a cytokine by a Th cell that is a cell specific to Survivin. The peptide can induce a Th cell that is specific to Survivin and can cause the production of a cytokine by the Sur/Th cell when the peptide is incubated together with an antigen-presenting cell and a CD4-positive T cell.


[Problem] To provide a polypeptide which enables stimulation of numerous T cells of different derivation, and to induce strong immunological response against numerous types of cancers. [Solution] Provided is a fused polypeptide that includes a helper epitope derived from the WT1 protein, and a killer epitope derived from the WT1 protein, wherein the polypeptide includes a total of 3 to 6 of the helper epitopes and the killer epitopes per molecule of the fused polypeptide.

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