Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06126 (CD1a)
2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transduction of dendritic cells (DCs) with genes encoding tumor-associated antigen or with other genes that enhance immune reaction has been theorized to be potentially useful for enhancing the efficiency of DC-based immunotherapy. However, gene transduction of DCs generated from human peripheral blood monocytes has been of limited use because of the low efficiency. Here, we report that the efficiency of in vitro adenovirus-mediated gene transduction into human monocyte-derived DCs can be dramatically enhanced by centrifugation. The best conditions for centrifugal gene transduction were determined to be as follows: 2000 x g at 37 degrees C for 2 hr at a multiplicity of infection (MOI) of 10 or greater. By this centrifugal method, approximately 88 and 70% of DCs were gene transducible at an MOI of 50 and 10, respectively. Functional analysis showed that DCs transduced with human interleukin 12 (IL-12)-expressing adenoviral vector under the optimal conditions of centrifugation stably produced IL-12 protein at high levels (8.1 ng/10(6) cells/48 hr). IL-12 gene-modified DCs (DC/IL-12) displayed a more mature phenotype than nontransduced DCs, as judged by decreased expression of CD1a and increased expression of CD83, B7.1 (CD80), B7.2 (CD86), and MHC class I and II molecules. DC/IL-12 showed a high phagocytic ability similar to nontransduced DCs and were significantly superior to control DCs in the stimulation of autologous and allogeneic T lymphocyte responses. The centrifugal transduction method with adenoviral vector might be useful for efficient generation of gene-modified DCs because it is very simple, highly efficient, reproducible, and not cytopathic. IL-12 gene-modified human DCs may be therapeutically useful as a good adjuvant in DC-based immunotherapy.
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PMID:Enhanced efficiency by centrifugal manipulation of adenovirus-mediated interleukin 12 gene transduction into human monocyte-derived dendritic cells. 1124 26

Dendritic cells (DCs) derived from bone marrow cells are specialized cells for the uptake, processing, and presentation of foreign and self-antigens. The study indicated that re-transfusion of DCs pulsed with tumor-associated antigen can induce an vigorous specific anti-tumor response in clinic. The present study was aimed to investigate the enhancing effect of DCs derived from human cord blood on T cells in killing tumor cells. Human cord blood mononuclear cells were isolated from human cord blood by density gradient centrifugation using lymphocyte separating medium, and cord blood mononuclear cells were obtained by adherence and cultured in a liquid culture system with GM-CSF and IL-4 for 15 days. Then the cells were analyzed for phenotypes of CD1a by indirect immunofluorescence. The capacity of DCs to initiate T cell-dependent anti-tumor immune responses was assayed by MTT kit. The ratios of DCs to tumor cells in experimental groups were 20:1, 50:1 and 100:1 respectively. The DCs were not added in control group. The results indicated that in the presence of GM-CSF and IL-4, the DCs with typical morphological features at days 15 were observed. At that time, (43.12 +/- 5.83)% CD1a(+) cells were obtained. In addition to these phenotypic properties, the DC of experimental groups could remarkably initiate T cell-dependent anti-tumor immune responses with different ratios compared with control group (P < 0.01), there were no significant difference of killing effects between 100:1 and 50:1 groups (P > 0.05), and killing effect of DC in 20:1 group was higher than that in 100:1 or 50:1 groups (P < 0.05). It is concluded that human cord blood mononuclear cells can serve as a better source of DC, which can promote the capacity to initiate T cell-dependent anti-tumor immune responses.
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PMID:[Enhancing effect of dendritic cells derived from human cord blood on T cells in killing tumor cells]. 1760 71