17 results on '"Gong, Jianlin"'
Search Results
2. Strategies to improve the immunogenicity of anticancer vaccines based on dendritic cell/malignant cell fusions.
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Shigeo Koido, Sadamu Homma, Masato Okamoto, Yoshihisa Namiki, Kazuki Takakura, Kan Uchiyama, Mikio Kajihara, Seiji Arihiro, Hiroo Imazu, Hiroshi arakawa, Shin Kan, Hideo Komita, Yuko Kamata, Masaki Ito, Toshifumi Ohkusa, Gong, Jianlin, and Hisao Tajiri
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ANTINEOPLASTIC agents ,DENDRITIC cells ,CELL fusion ,TUMOR antigens ,CYTOTOXIC T cells ,MESSENGER RNA - Abstract
The rationale for fusing dendritic cells (DCs) with whole tumor cells to generate anticancer vaccines resides in the fact that the former operate as potent antigen-presenting cells, whereas the latter express a constellation of tumor-associated antigens (TAAs). although the administration of DC/malignant cell fusions to cancer patients is safe and this immunotherapeutic intervention triggers efficient tumor-specific T-cell responses in vitro, a limited number of objective clinical responses to DC/cancer cell fusions has been reported thus far. This review discusses novel approaches to improve the immunogenicity of DC/malignant cell fusions as anticancer vaccines. [ABSTRACT FROM AUTHOR]
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- 2013
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3. Cellular and molecular chaperone fusion vaccines: Targeting resistant cancer cell populations.
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Calderwood, Stuart K., Gong, Jianlin, Stevenson, Mary Ann, and Murshid, Ayesha
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MOLECULAR chaperones , *CANCER treatment , *CANCER vaccines , *DENDRITIC cells , *T cells , *ANIMAL models in research , *VACCINES , *THERAPEUTICS - Abstract
Molecular chaperone-based vaccines offer a number of advantages for cancer treatment. We have discussed the deployment of a vaccine prepared by gentle isolation of Hsp70 from tumour dendritic cell fusions (Hsp70 fusion vaccine). The vaccine was highly effective in triggering specific T cell immunity and in the treatment of tumour-bearing mice and the preparation was shown to retain an increased amount of tumour antigens compared to other chaperone-based isolates. This approach has the further advantage that tumour sub-populations could be used to prepare the Hsp70 fusion vaccine. Cellular fusion vaccines were made to specifically target drug-resistant cancer cells and tumour cell populations enriched in ovarian cancer stem cells (CSC). Such vaccines showed enhanced capacity to trigger T cell immunity to these resistant ovarian carcinoma populations. We have discussed the potential of using the cellular and Hsp70 fusion vaccine approaches in therapy of treatment-resistant cancer cells and its deployment in combination with ionising radiation or hyperthermia to enhance the effectiveness of both forms of therapy. [ABSTRACT FROM AUTHOR]
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- 2013
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4. Regulation of Tumor Immunity by Tumor/Dendritic Cell Fusions.
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Homma, Sadamu, Takahara, Akitaka, Hara, Eiichi, Nagasaki, Eijiro, Komita, Hideo, Tajiri, Hisao, Gong, Jianlin, Ito, Masaki, Koido, Shigeo, Ohkusa, Toshifumi, and Namiki, Yoshihisa
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TUMORS ,IMMUNITY ,DENDRITIC cells ,IMMUNE response ,T cells ,ANTIGENS ,VACCINES - Abstract
The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment. [ABSTRACT FROM AUTHOR]
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- 2010
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5. Cancer Vaccine by Fusions of Dendritic and Cancer Cells.
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Koido, Shigeo, Hara, Eiichi, Homma, Sadamu, Namiki, Yoshihisa, Ohkusa, Toshifumi, Gong, Jianlin, and Tajiri, Hisao
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CANCER vaccines ,DENDRITIC cells ,CANCER cells ,FUSION (Phase transformation) ,IMMUNE response - Abstract
Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination. [ABSTRACT FROM AUTHOR]
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- 2009
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6. In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells.
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Koido, Shigeo, Homma, Sadamu, Hara, Eiichi, Mitsunaga, Makoto, Namiki, Yoshihisa, Takahara, Akitaka, Nagasaki, Eijiro, Komita, Hideo, Sagawa, Yukiko, Ohkusa, Toshifumi, Fujise, Kiyotaka, Gong, Jianlin, and Tajiri, Hisao
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T cells ,DENDRITIC cells ,LIVER cancer ,CANCER cells ,CELL culture ,ANTIGENS - Abstract
Background: Human hepatocellular carcinoma (HCC) cells express WT1 and/or carcinoembryonic antigen (CEA) as potential targets for the induction of antitumor immunity. In this study, generation of cytotoxic T lymphocytes (CTL) and regulatory T cells (Treg) by fusions of dendritic cells (DCs) and HCC cells was examined. Methods: HCC cells were fused to DCs either from healthy donors or the HCC patient and investigated whether supernatants derived from the HCC cell culture (HCCsp) influenced on the function of DCs/HCC fusion cells (FCs) and generation of CTL and Treg. Results: FCs coexpressed the HCC cells-derived WT1 and CEA antigens and DCs-derived MHC class II and costimulatory molecules. In addition, FCs were effective in activating CD4
+ and CD8+ T cells able to produce IFN-γ and inducing cytolysis of autologous tumor or semiallogeneic targets by a MHC class I-restricted mechanism. However, HCCsp induced functional impairment of DCs as demonstrated by the down-regulation of MHC class I and II, CD80, CD86, and CD83 molecules. Moreover, the HCCsp-exposed DCs failed to undergo full maturation upon stimulation with the Toll-like receptor 4 agonist penicillin-inactivated Streptococcus pyogenes. Interestingly, fusions of immature DCs generated in the presence of HCCsp and allogeneic HCC cells promoted the generation of CD4+ CD25high Foxp3+ Treg and inhibited CTL induction in the presence of HCCsp. Importantly, up-regulation of MHC class II, CD80, and CD83 on DCs was observed in the patient with advanced HCC after vaccination with autologous FCs. In addition, the FCs induced WT1- and CEA-specific CTL that were able to produce high levels of IFN-γ. Conclusion: The current study is one of the first demonstrating the induction of antigen-specific CTL and the generation of Treg by fusions of DCs and HCC cells. The local tumor-related factors may favor the generation of Treg through the inhibition of DCs maturation; however, fusion cell vaccination results in recovery of the DCs function and induction of antigen-specific CTL responses in vitro. The present study may shed new light about the mechanisms responsible for the generation of CTL and Treg by FCs. [ABSTRACT FROM AUTHOR]- Published
- 2008
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7. Induction of anti-leukemic cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous myeloblasts
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Gong, Jianlin, Koido, Shigeo, Kato, Yoko, Tanaka, Yasuhiro, Chen, Dongshu, Jonas, Anna, Galinsky, Ilene, DeAngelo, Daniel, Avigan, David, Kufe, Donald, and Stone, Richard
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DENDRITIC cells , *LEUCOCYTES , *IMMUNE system , *LYMPHOCYTES , *IMMUNOTHERAPY , *T cells - Abstract
Presentation of AML antigens by dendritic cells (DC) could potentially induce a T cell-mediated anti-leukemic immune response. In the present study, we generated DC from adherent (AD-DC) and non-adherent (NAD-DC) myeloblasts obtained from bone marrows of AML patients. Both cell populations displayed morphological, phenotypic and functional properties of DC. The functions of NAD-DC were compared to AD-DC that had been fused with autologous AML blasts (FC/AML). The FC/AML induced greater T cell proliferation and CTL activity against autologous AML blasts (9/10 cases) as compared to NAD-DC. FC/AML may thus represent a promising strategy for DC-based immunotherapy of patients with AML. [Copyright &y& Elsevier]
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- 2004
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8. research paper Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma.
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Raje, Noopur, Hideshima, Teru, Davies, Faith E., Chauhan, Dharminder, Treon, Steven P., Young, Gloria, Tai, Yu-Tzu, Avigan, David, Gong, Jianlin, Schlossman, Robert L., Richardson, Paul, Kufe, Donald W., and Anderson, Kenneth C.
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IMMUNOTHERAPY ,CANCER cells ,DENDRITIC cells ,VACCINES ,MULTIPLE myeloma ,LYMPHOCYTES ,T cells - Abstract
Multiple myeloma (MM) cells express certain tumour-associated antigens (TAAs) that could serve as targets for active-specific immunotherapy. The aim of the present study was to test the MM/dendritic cell (DC) fusion as a vaccination strategy. We fused MM cells with DC to generate fusion cells (FCs) and tested their antigen presenting cell (APC) function in mixed lymphocyte reactions and cytotoxicity assays. First, the HS Sultan and SK0-007 HAT sensitive human MM cell lines and DCs generated from peripheral blood of normal donors were fused in the presence of 50% polyethylene glycol to form FCs. Next, tumour cells freshly isolated from patients were similarly fused with autologous DCs to generate FCs. The FCs demonstrated a biphenotypic profile, confirmed both by flow-cytometry and dual immunofluorescence microscopy. These FCs induced MM-specific cytotoxicity. FCs, but not MM cells or DCs alone, were potent stimulators of autologous patient T cells. More importantly, FC-primed autologous peripheral blood mononuclear cells demonstrated major histocompatibility complex-restricted MM-specific cytolysis. These studies therefore demonstrated that MM/DC FC can trigger an autologous immune response to MM cells and formed the framework for a clinical trial currently underway. [ABSTRACT FROM AUTHOR]
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- 2004
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9. Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice.
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Homma, Sadamu, Toda, Gotaro, Gong, Jianlin, Kufe, Donald, Ohno, Tsuneya, Homma, S, Toda, G, Gong, J, Kufe, D, and Ohno, T
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LIVER cancer ,DENDRITIC cells ,THERAPEUTICS - Abstract
Background: The prevention of recurrence of hepatocellular carcinoma (HCC) after treatment is very important for improvement of the prognosis of HCC patients. Dendritic cells (DCs) are potent antigen-presenting cells that can prime naive T cells to induce a primary immune response. We attempted to induce preventive antitumor immunity against HCC by immunizing BALB/c mice with fusions of DCs and HCC cells.Methods: Murine bone marrow-derived DCs and a murine HCC cell line. BNL cells, were fused by treatment with 50% polyethyleneglvcol (PEG). Fusion efficacy was assessed by the analysis of fusions of BNL cells stained with red fluorescent dye and DCs stained with green fluorescent dye. Mice injected intravenously with DC/BNL fusions were challenged by BNL cell inoculation.Results: About 30% of the PEG-treated non-adherent cells with both fluorescences were considered to be fusion cells. The cell fraction of DC/BNL fusions showed phenotypes of DCs, MHC class II, CD80, CD86, and intercellular adhesion molecule (ICAM)-1, which were not expressed on BNL cells. Mice immunized with the fusions were protected against the inoculation of BNL tumor cells, whereas injection with a mixture of DCs and BNL cells not treated with PEG did not provide significant resistance against BNL cell inoculation. Splenocytes from DC/BNL fusion-immunized mice showed lytic activity against BNL cells.Conclusions: These results demonstrate that immunization with fusions of DCs and HCC cells is capable of inducing preventive antitumor immunity against HCC. [ABSTRACT FROM AUTHOR]- Published
- 2001
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10. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells.
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Gong, Jianlin and Avigan, David
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CANCER cells , *DENDRITIC cells , *T cells - Abstract
Presents information on a study which demonstrated fusions of human breast cancer cells and dendritic cells (DC) activate T cell responses against autologous tumors. Function of breast tumor cell/DC fusions; Materials and methods of the study; Phenotype of human breast tumor cell/DC fusions; Results and discussion.
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- 2000
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11. The combination of TLR2 and TLR4 agonists promotes the immunogenicity of dendritic cell/cancer cell fusions.
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Shigeo Koido, Sadamu Homma, Masato Okamoto, Yoshihisa Namiki, Kazuki Takakura, Kan Uchiyama, Mikio Kajihara, Toshifumi Ohkusa, Gong, Jianlin, and Hisao Tajiri
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CHEMICAL agonists ,DENDRITIC cells ,CANCER cells ,IMMUNE response ,IMMUNOSUPPRESSIVE agents - Abstract
The induction of antitumor immune responses by dendritic cell (DC)/tumor cell fusions can be modulated by their activation status. Our recent work reveals that the combination of toll-like receptor 2 (TLR2) and TLR4 agonists promotes the immunogenicity of DC/tumor cell fusions, allowing them to overcome the immunosuppressive efects of transforming growth factor β1. [ABSTRACT FROM AUTHOR]
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- 2013
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12. Chemoimmunotherapy targeting Wilms’ tumor 1 (WT1)-specific cytotoxic T lymphocyte and helper T cell responses for patients with pancreatic cancer.
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Koido, Shigeo, Homma, Sadamu, Okamoto, Masato, Takakura, Kazuki, Gong, Jianlin, Sugiyama, Haruo, Ohkusa, Toshifumi, and Tajiri, Hisao
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PANCREATIC cancer ,T cells ,IMMUNOTHERAPY ,DENDRITIC cells ,EPITOPES ,CANCER chemotherapy - Abstract
We designed a phase 1 study using dendritic cells (DCs) pulsed with a mixture of three types of Wilms’ tumor 1 (WT1) peptides, including MHC class I/II restricted epitopes (DC/WT1-I/II). Our recent work reveals that the combination of DC/WT1-I/II and chemotherapy induced long-term WT1-specific CD4+and CD8+T cell responses. [ABSTRACT FROM AUTHOR]
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- 2014
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13. Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1-positive carcinoma cells.
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Chen, Dongshu, Xia, Jianchuan, Tanaka, Yasuhiro, Chen, Hongsong, Koido, Shigeo, Wernet, Oliver, Mukherjee, Pinku, Gendler, Sandra J., Kufe, Donald, and Gong, Jianlin
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MAMMARY gland cancer ,IMMUNOTHERAPY ,DENDRITIC cells ,MUCINS - Abstract
Summary The tumour-associated antigen mucin 1 (MUC1) is a multifunctional protein involved in protection of mucous membranes, signal transduction, and modulation of the immune system. More than 70% of cancers overexpress MUC1, making MUC1 a potential target for immunotherapy. In the present study, MUC1 transgenic mice were crossed with syngeneic strains that express the polyomavirus middle-T oncogene (PyMT) driven by the mouse mammary tumour virus promoter long-terminal repeat (MMTV-LTR). The resultant breed (MMT mice) developed spontaneous MUC1-expressing mammary carcinomas with 100% penetrance at 8–15 weeks of age. As found in human breast cancer, the mammary carcinoma in MMT mice arose in multiple stages. Immunization with fusions of dendritic cells and MUC1-positive tumour cells (FC/MUC1) induced MUC1-specific immune responses that blocked or delayed the development of spontaneous breast carcinomas. In contrast, there was no delay of tumour development in MMT mice immunized with irradiated MC38/MUC1 tumour cells. The efficacy of fusion cells was closely correlated with the timing of initial immunization. Immunization with FC/MUC1 initiated in MMT mice at < 1, 1–2 and 2–3 months of age rendered 33, 5 and 0% of mice free of tumour, respectively, up to 6 months. Whereas mice immunized in the later stage of tumour development succumbed to their disease, immunization resulted in control of tumour progression and prolongation of life. These results indicate that immunization with FC/MUC1 can generate an anti-MUC1 response that is sufficient to delay the development of spontaneous mammary carcinomas and control tumour progression in MMT mice. [ABSTRACT FROM AUTHOR]
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- 2003
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14. Dendritic/pancreatic carcinoma fusions for clinical use: Comparative functional analysis of healthy- versus patient-derived fusions
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Koido, Shigeo, Hara, Eiichi, Homma, Sadamu, Namiki, Yoshihisa, Komita, Hideo, Takahara, Akitaka, Nagasaki, Eijiro, Ito, Masaki, Sagawa, Yukiko, Mitsunaga, Makoto, Uchiyama, Kan, Satoh, Kenichi, Arihiro, Seiji, Ohkusa, Toshifumi, Gong, Jianlin, and Tajiri, Hisao
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PANCREATIC cancer , *DENDRITIC cells , *CANCER cells , *BLOOD proteins , *COMPARATIVE studies , *TRANSFORMING growth factors , *INTERLEUKINS , *METASTASIS - Abstract
Abstract: Fetal calf serum (FCS)-independent pancreatic cancer cells were established in plasma protein fraction (PPF)-supplemented medium that is an agent of good manufacturing practice (GMP) grade. Dendritic cells (DCs) were activated with the Toll-like receptor agonist, penicillin-inactivated Streptococcus pyogenes (OK-432) that is also a GMP grade agent. Therefore, sufficient amounts of FCS-independent fusions were successfully generated with decreased potential hazards of FCS. The FCS-independent fusions expressed tumor-associated antigens, HLA-DR, costimulatory molecules, IL-12, and IL-10. Stimulation of T cells with fusions from healthy donors resulted in proliferation of T cells with high expression levels of perforin/granzyme B and IFN-γ and efficient induction of antigen-specific cytotoxic T lymphocytes (CTLs). Selection and expansion of T-cell clones were confirmed by TCR Vβ analysis. However, fusions from patients with metastatic pancreatic cancer induced increased expression levels of TGF-β1 in CD4+ CD25high T cells and low levels of CTLs with decreased IFN-γ production. [Copyright &y& Elsevier]
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- 2010
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15. Generation and functional assessment of antigen-specific T cells stimulated by fusions of dendritic cells and allogeneic breast cancer cells
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Koido, Shigeo, Tanaka, Yasuhiro, Tajiri, Hisao, and Gong, Jianlin
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T cells , *IMMUNOTHERAPY , *DENDRITIC cells , *CANCER cells , *THERAPEUTICS - Abstract
Abstract: We have reported that fusions of patient-derived dendritic cells (DC) and autologous breast cancer cells induce T-cell responses against autologous tumors. However, the preparation of fusion cells requires patient-derived tumor cells, and these are not always available in the clinical setting. In the present study, we explore an alternative approach to constructing DC-breast cancer fusion vaccine by using breast caner-cell lines. DC generated from HLA-A*0201-positive donor were fused to HLA-A*0201+ allogeneic MCF7 breast cancer cells. These fusion cells co-expressed tumor-associated antigens and DC-derived costimulatory and MHC molecules. Both CD4 and CD8 T cells were activated by the fusion cells as demonstrated by the production of IFN-γ. The fusion cells induced strong antigen-specific cytotoxic T lymphocytes (CTL) activity against their parent cells. The lysis of targets was restricted by HLA-A*0201, since killing was blocked by the anti-HLA-A2 mAb. Similar CTL activity against HLA-A*0201-positive targets was induced when T cells were cocultured with fusions of DC and HLA-A*0201-negative allogeneic BT20 breast cancer cells. In addition, administration of T cells stimulated by DC-breast cancer fusion cells regressed 7-day-old tumors and rendered mice free of disease up to 90 days. These results suggest that tumor-cell lines can be used as a fusion partner in the construction of DC-tumor fusion vaccine. Such fusion cells hold promise since they can be used as a vaccine for active immunotherapy or as stimulators to activate and expand T cells for adoptive immunotherapy. [Copyright &y& Elsevier]
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- 2007
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16. Assessment of fusion cells from patient-derived ovarian carcinoma cells and dendritic cells as a vaccine for clinical use
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Koido, Shigeo, Nikrui, Najmosama, Ohana, Masaya, Xia, Jianchuan, Tanaka, Yasuhiro, Liu, Chunlei, Durfee, John K., Lerner, Adam, and Gong, Jianlin
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OVARIAN cancer , *T cells , *LYMPHOCYTES , *DENDRITIC cells - Abstract
Abstract: Purpose. : To evaluate a protocol that allowed the successful generation of DC and OVCA cells, fusion of these two cell types and assessment of stimulatory ability of the fusion cells for clinical use. Patients and methods. : Ovarian cancer (OVCA) cells and dendritic cells (DC) were isolated or generated from 22 patients with OVCA and subsequently fused with PEG. The stimulatory ability of fusion cells including T cell proliferation and induction of cytotocic T lymphocytes (CTL) was assessed. In addition, the impact of radiation, freezing and thawing of the fusion cells was evaluated. Results. : OVCA cells derived from 22 patients were successfully fused with autologous DC. The created heterokaryons expressed tumor-associated antigens, such as MUC1 and CA-125, and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, CD4 and CD8 T cells derived from patients with ovarian cancer were stimulated by fusion cells and produced IFN-γ as demonstrated with intracellular staining. Significantly, T cells primed by fusion cells produced MHC class I-dependent lysis of autologous ovarian tumor cells. One cycle of fusion-cell stimulation can maintain the CTL activity up to 25 days. Conclusions. : The fusion of human OVCA cells and DC created immunogenic cells capable of stimulating CD4 and CD8 T cells. The effects of the processes required for preparing a vaccine for clinical use, including freezing and thawing and irradiation, do not interfere with the immunogenic properties of the fusion cells. [Copyright &y& Elsevier]
- Published
- 2005
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17. Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation
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Koido, Shigeo, Ohana, Masaya, Liu, Chunlei, Nikrui, Najmosama, Durfee, John, Lerner, Adam, and Gong, Jianlin
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DENDRITIC cells , *ANTIGEN presenting cells , *TUMOR antigens , *TUMOR markers , *T cells - Abstract
Fusion of human dendritic cells (DC) with tumor cells is an effective approach for delivering tumor antigens to DC, and DC/tumor fusion cells are potent stimulators of autologous T cells. However, the integration and morphology of DC/tumor fusion cells has not been examined. In the present study, we fused patient-derived DC to autologous breast or ovarian carcinoma cells. The fusion cells possessed the properties of both parent cells. After fusion, the cytoplasm of the two cells was integrated, whereas their nuclei remained separate entities. Colocalization of MUC1 peptide and HLA-DR molecules was observed on fusion cells under the immunoelectron microscope. Coculture of patient-derived peripheral blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in activation of CD4 and CD8 T cells as assessed by IFN-γ secretion, HLA-A*0201-MUC1 tetramer, and standard cytotoxic T lymphocyte (CTL) assays. The present study provides first evidence of integration of human DC and tumor cells and links their properties to T cell activation. [Copyright &y& Elsevier]
- Published
- 2004
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