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Zhang X.,Institute of Hematopoietic Stem Cell of PLA | Xu H.,Central Hospital of Jinhua | Zhang B.,Institute of Hematopoietic Stem Cell of PLA | Chen H.,Institute of Hematopoietic Stem Cell of PLA
Chinese Journal of Cancer Biotherapy | Year: 2013

Objective: To construct a recombinant adenovirus Ad5/F35 containing human melanoma-associated antigen 3 (MAGE-A3), and to observe the effect of adenovirus-mediated MAGE-A3 overexpression on the maturation and apoptosis of dendritic cells (DCs) in patients with melanoma. Methods: To choose the adenoviral vectors with the highest transfection efficiency, and then to construct recombinant adenovirus vectors and packaging adenovirus particles Ad5/F35-MAGE-A3. Immunohistochemistry and Western blotting were performed to detect the influence of Ad5/F35-MAGE-A3 infection on the expression of MAGE-A3 of DCs in healthy people and patients with kidney cancer or melanoma. Flow cytometry was used to detect the effect of Ad5/F35-MAGE-A3 infection on the maturation and apoptosis of DCs in patients with melanoma. Results: The recombinant adenovirus vector containing human MAGE-A3 was successfully constructed and adenovirus particles Ad5/F35-MAGE-A3 were packaged with the infective titer of 7.94 × 108 IU/ml. Ad5/F35-MAGE-A3 infection improved the MAGE-A3 expression of DCs in healthy people and kidney cancer patients (P<0.05), and it did not affect MAGE-A3 expression of DCs in melanoma patients ([0.3352±0.1272] vs [0.4672±0.0704], P>0.05). After Ad5/F35-MAGE-A3 infection, the co-stimulatory molecule CD80 ([20.42±0.58]% vs [10.22±1.04]%, [8.95±0.2]%), CD86 ([85.3±3.98]% vs [39.85±2.86]%, [34.1±4.32]%) and HLA-DR ([86.87±4.36]% vs [63.68±3.15]%, [60.69 ±4.81]%) which expressed on the surface of DCs was significantly higher than that of the negative control group and the blank control group (all P<0.05), but no significant difference existed in apoptosis rate ([1.18±0.09]% vs[1.09±0.11]%, P>0.05). Conclusion: Recombinant adenovirus vector can efficiently affect DCs. Ad5/F35-MAGE-A3 infection may not affect the expression of MAGE-A3 of DCs in melanoma patients, and promote the maturation of DCs without obvious cytotoxicity. Source


Bin Z.,Institute of Hematopoietic Stem Cell of PLA | Hu C.,Institute of Hematopoietic Stem Cell of PLA
Chinese Journal of Cancer Biotherapy | Year: 2015

Among the various available cancer treatment modalities, anti-tumor immune escape is attracting tremendous attention worldwide and has become one of the fast-developing research fields, especially when the anti-prostate cancer vaccine was approved by the FDA and the monocloan antibodies, which targeted PD-1 and CTLA-4, were successfully launched into market. Since 2010, tremendous research progress has been made on cellular immunotherapy of cancer in China. Nevertheless, practically cellular immunotherapy of cancer is facing several challenging issues. Including: 1) how to choose the proper treatment modality and time duration; 2) how to manage the quality control; 3) how to evaluate the treatment outcome; and 4) how to obtain stronger empirical evidence to support the benefits of the treatment. With regard to quality management and outcome evaluation, there exist similarities and differences between cellular immunotherapy and traditional biological and chemical drugs for cancers. Similar to the quality control of biological and chemical treatments of cancer, the quality management of cellular immunotherapy of cancer involves such aspects as the structure of the clinic or center, personnel training and testing program. In contrast, the outcome evaluation of cellular immunotherapy of cancer cannot simply follow the traditional method for biological and chemical cancer therapies. This paper aims to review the recent development in the quality management and outcome evaluation of cellular immunotherapy of cancer, hoping to bring these issues to the attention of peers in China. © 2015, Editorial office of Chinese Journal of Cancer Biotherapy. All rights reserved. Source

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