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1.
Mol Cancer Ther ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582530

RESUMO

Viral-based CAR T cell manufacturing has potential safety risks and relatively high costs. The non-viral minicircle DNA (mcDNA) is safer for patients, cheaper to produce, and may be a more suitable technique to generate CAR T cells. In this study, we produced mcDNA-based CAR T cells specifically targeting PSCA (mcDNA-PSCA-CAR T cells). Our results showed that mcDNA-PSCA-CAR T cells persisted in mouse peripheral blood as long as 28 days and demonstrated more CAR T cell infiltration, higher cytokine secretion levels, and better anti-tumor effects. Together, our results suggest that mcDNA-CAR can be a safe and cost-effective platform to produce CAR T cells.

2.
Immunotherapy ; 11(7): 599-616, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30943862

RESUMO

AIM: To produce dendritic cells (DCs) from CD34+ stem cells from cord blood and explore their prophylactic and curative effect against tumors by vaccinating humanized NSG mice. MATERIALS & METHODS: Separated CD34+ stem cells from cord blood were cultured for 30 days, and the resultant DCs (CD34-DCs) were collected. The basic function of the CD34-DCs and the cytotoxicity of CD34-cytotoxic-T lymphocytes (CTLs) were tested in vitro, and tumor inhibition in a humanized NSG mouse tumor model was observed. RESULTS: The number of CD34-DCs reached approximately 9 log. These cells performed functions similar to those of DCs derived from monocytes from peripheral blood (PBMC-DCs). The CTLs of the CD34-DCs (CD34-CTLs) presented a better antitumor effect in vitro. The obvious prophylactic and therapeutic antitumor effects of the CD34-DC vaccine were observed in the humanized NSG mouse models. CONCLUSION: CD34-DCs from cord blood were sufficient in quantity and quality as a vaccine agent against tumors in vitro and in vivo.

4.
Oncotarget ; 9(4): 5208-5215, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29435173

RESUMO

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that functions to attenuate T cell activation. In this study, we knocked out (KO) PD-1 in cytotoxic T lymphocytes (CTLs) using CRISPR-Cas9 system to evaluate its effect on the anti-tumor activity of the CTLs against multiple myeloma (MM). Results show that PD-1 KO CTLs facilitate apoptosis and caspase activation of the co-cultured MM cells and enhanced MM cell death by 36% compared with the control. PD-1 KO also increased TNF-α and IFN-γ secretion of the CTLs by 2.4 and 1.9-fold respectively. The effectiveness of PD-1 KO in enhancing anti-tumor activity of the CTLs was verified in vivo using mouse xenograft model. The xenografted mice treated with PD-1 KO CTLs demonstrated repressed MM tumor growth and prolonged survival compared with the control group. We conclude that CRISPR-Cas9 is an efficient system to knock out PD-1 from CTLs and PD-1 KO could significantly enhance the anti-tumor activity of CTLs.

5.
Ann Clin Lab Sci ; 48(6): 805-807, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30610055

RESUMO

A 71-year-old woman presented with acute monocytic leukemia with lymphoma-like morphologic features and an unusual complex karyotype. Bone marrow (BM) aspiration revealed acute monocytic leukemia with lymphoma-like morphologic features. Thus, we called the condition a lymphoma presentation. The patient was diagnosed with acute monocytic leukemia (AML FAB M5a) according to the French-American-British (FAB) classification and the new World Health Organization (WHO) classification [1]. To our knowledge, this is the first reported case of an unusual complex karyotype in acute monocytic leukemia with a lymphoma presentation and adds to the expanding list of karyotypic abnormalities seen in acute monocytic leukemia. We present the case given its rarity, occasional misdiagnosis and poor prognosis. Whether this complex karyotype resulted in such lymphoma-like morphologic features remains to be determined. The case illustrates the importance of the morphologic features cognition and avoiding misdiagnosis. Clinical trials are available to further explore how to extend survival time and contribute to a better prognosis for patients suffering from acute monocytic leukemia with a complex karyotype.


Assuntos
Aberrações Cromossômicas , Cariotipagem/métodos , Leucemia Monocítica Aguda/patologia , Linfoma/patologia , Idoso , Antígenos CD/metabolismo , Feminino , Humanos , Leucemia Monocítica Aguda/complicações , Linfoma/complicações
6.
Oncol Lett ; 12(5): 3045-3050, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27899961

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and has a very poor prognosis. Its occurrence has been on the increase in recent years. Surgical resection and liver transplantation are the primary methods of treatment for HCC patients, but can only be applied to 15% of patients. The median survival time of unresectable or metastasizing HCC patients is only a few months. Existing systemic treatment methods are not effective for advanced HCC patients and a new method of treatment is needed for these patients. It has been established that the HCC occurs in multiple stages, however, the pathogenesis at a molecular level is not clear and many key factors are yet to be determined. In the past 30 years, it has become evident that the Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway plays a significant role in the occurrence and development of HCC. This review focused on the association between the Ras/Raf/MEK/ERK signaling pathway and HCC.

7.
Zhonghua Wai Ke Za Zhi ; 44(7): 476-80, 2006 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-16772085

RESUMO

OBJECTIVE: To investigate the antitumor effects of cytotoxic T lymphocytes (CTLs) induced by autologous dendritic cells that were inspired by autologous tumor lysates (ATLs-mDCs). METHODS: Primary gastric cancer cells prepared by short-term culture were used as targets. ATLs-mDCs were subjected to activate autologous T cells to generate CTLs. The immunological functions of DCs were evaluated by flow cytometry and by mixed leukocyte response (MLR) assay. The antitumor outcome of tumor antigen specific CTLs was tested by cytotoxicity assay. Concentrations of IL-12 in cultured DCs and INF-gamma in CTLs were measured by ELISA. RESULTS: The expressions of MHC-II, CD80, CD83 and CD86 were significantly up-regulated in ATLs-mDCs, moreover, the ATLs-mDCs obtained the capability of stimulating the proliferation of autologous T cells with high efficiency. The secretion of IL-12 in ATLs-mDCs was significantly higher than that in pure mature DCs (t = 15.47, P < 0.01) and in immature DCs (t = 28.44, P < 0.01). The secretion of INF-gamma in CTLs activated by ATLs-mDCs was significantly higher than that in CTLs by pure mature DCs (t = 4.84, P < 0.05) and in CTLs by immature DCs (t = 13.74, P < 0. 01). The antigen specific cytotoxicity of CTLs induced by ATLs-mDCs was significantly higher against autologous tumor cells [(84 +/- 11)%] than that against two allogeneic tumor cell lines [(19 +/- 7)% and (19 +/- 11)%; t = 54.18 and 56.46, P < 0.01, respectively]. CONCLUSIONS: ATLs-mDCs might mediate the antigen specific CTLs against autologous gastric cancer cells ex vivo with high efficiency.


Assuntos
Células Dendríticas/imunologia , Imunoterapia Adotiva/métodos , Neoplasias Gástricas/terapia , Linfócitos T Citotóxicos/imunologia , Citotoxicidade Imunológica , Humanos , Técnicas In Vitro , Interferon gama/metabolismo , Interleucina-12/metabolismo
8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 22(1): 92-5, 2006 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-16388755

RESUMO

AIM: To explore the efficiency of antitumor immunity induced by autologous dendritic cells (DCs) transfected with total RNA of autologous gastric cancer cells. METHODS: Short-term cultured primary gastric cancer cells were prepared. DCs in peripheral blood mononuclear cells (PBMCs) from gastric cancer patients were induced with rhGM-CSF, rhIL-4 and TNF-alpha. The mature DCs transfected with total RNA of autologous gastric cancer cells were subjected to activate autologous T cells transforming into CTLs, and the activity of CTLs was detected by using CCK-8 kit. The immunological function of DCs were evaluated by flow cytometry and mixed lymphocyte culture(MLC) assay. The levels of IFN-gamma and IL-12 were detected by ELISA. RESULTS: Mature DCs transfected with total RNA of autologous gastric cancer cells not only highly expressed costimulatory molecules (CD80, CD83 and CD86) and (MHC-I and MHC-II), but also powerfully stimulated allogenic or autologous T cell proliferation. The level of IL-12 secreted by mature DCs transfered with tumor RNA was notably higher than those secreted by untransfered and immature DCs, and the rate of killing autologous gastric cancer cells by CTLs was markedly higher than that of killing allogenic tumor cells. CONCLUSION: Mature DCs transfected with autologous gastric cancer cell total RNA can induce and activate high antigen-specific CTLs directed at autologous gastric cancer cells in vitro.


Assuntos
Citotoxicidade Imunológica/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Imunoterapia/métodos , RNA/genética , Neoplasias Gástricas/terapia , Antígenos CD/metabolismo , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Citotoxicidade Imunológica/genética , Humanos , Imunoglobulinas/metabolismo , Interleucina-12/metabolismo , Glicoproteínas de Membrana/metabolismo , Microscopia de Contraste de Fase , Neoplasias Gástricas/genética , Células Tumorais Cultivadas
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