The open gene therapy journal最新文献_第2页

Anti-Tumor Activity of Genetically Redirected T Cells Against Orthotopic Kidney Cancer in Mice~!2010-01-06~!2010-03-24~!2010-05-13~! 基因重定向T细胞对小鼠原位肾癌的抗肿瘤活性研究2010-01-06 2010-03-24 2010-05-13

The open gene therapy journal Pub Date : 2010-05-13 DOI: 10.2174/1875037001003010001

J. Westwood, Preethi Mayura-Guru, W. Murray, H. Pegram, Sally M. Amos, Carol L. Van Puyenbroek, R. Cameron, M. Smyth, Yuekang Xu, P. Darcy, M. Kershaw

{"title":"Anti-Tumor Activity of Genetically Redirected T Cells Against Orthotopic Kidney Cancer in Mice~!2010-01-06~!2010-03-24~!2010-05-13~!","authors":"J. Westwood, Preethi Mayura-Guru, W. Murray, H. Pegram, Sally M. Amos, Carol L. Van Puyenbroek, R. Cameron, M. Smyth, Yuekang Xu, P. Darcy, M. Kershaw","doi":"10.2174/1875037001003010001","DOIUrl":"https://doi.org/10.2174/1875037001003010001","url":null,"abstract":"In order to test the effectiveness of adoptive immunotherapy against renal cell carcinoma (RCC) in a mouse model relevant to human disease, we first generated two murine renal cell carcinoma cell lines expressing the human tumor-associated antigen erbB2 by genetic modification of the Renca and SIRCC cell lines. When injected into the kidneys of mice, these cell lines rapidly formed a primary kidney tumor that metastasized to lung, liver and various peritoneal locations. Tumor-specific mouse T cells were generated by genetic modification of splenic T cells in vitro. The transgene encoded a chimeric receptor (T-body) specific for erbB2, in which a single-chain (scFv) anti-erbB2 antibody was linked to T cell activation and costimulatory domains (scFv-erbB2-CD28-zeta), to enable tumor recognition in a major histocompatibility complex-independent manner. Gene-modified T cells expressed the T-body on their surface, and could respond specifically against erbB2-expressing tumor cells as demonstrated by secretion of interferon-gamma. Adoptive transfer of T-body-expressing T cells could lead to inhibition of primary tumor and metastases. Systemic delivery of these gene-modified T cells led to complete eradication of disease in a proportion of mice, and this was associated with peri-vascular tissue inflammation composed of activated lymphoid cells, with macrophages and lesser numbers of eosinophils and neutrophils. This study demonstrated, for the first time, the efficacy of genetically redirected T cells against orthotopic renal cell carcinoma in mice.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"3 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2010-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human Mesenchymal Stem Cells (MSC) Indirectly Preserve Liver of Irradiation Damage 人间充质干细胞(MSC)间接保护肝脏辐照损伤

The open gene therapy journal Pub Date : 2009-08-18 DOI: 10.2174/1875037000902010045

M. Mouiseddine, S. Francois, A. Sémont, Amandine Sache Christelle Demarqua, A. Athias, P. Gourmelon, N. Gorin, M. Souidi, A. Chapel

{"title":"Human Mesenchymal Stem Cells (MSC) Indirectly Preserve Liver of Irradiation Damage","authors":"M. Mouiseddine, S. Francois, A. Sémont, Amandine Sache Christelle Demarqua, A. Athias, P. Gourmelon, N. Gorin, M. Souidi, A. Chapel","doi":"10.2174/1875037000902010045","DOIUrl":"https://doi.org/10.2174/1875037000902010045","url":null,"abstract":"The present work was initiated in an effort to evaluate the potential therapeutic contribution of the infusion of MSC for the correction of liver injuries. We subjected NOD-SCID mice to a 10.5 Gy abdominal irradiation and we tested the biological and histological markers of liver injury in the absence and after infusion of expanded human MSC. Irradiation alone induced a significant elevation of transaminases (ALT and AST). Apoptosis in the endothelial layer of vessels was observed. When MSC were infused in mice, a significant decrease of transaminases was measured, and a total disappearance of apoptotic cells. MSC were not found in liver. To explain the protection of liver without MSC en- graftment, we hypothesize an indirect action of MSC on the liver via the intestinal tract. Pelvic or total body irradiation induces intestinal absorption defects leading to an alteration of the enterohepatic recirculation of bile acids. This alteration induces an increase in Deoxy Cholic Acid (DCA) which is hepatoxic. In the present study, we confirm these results. DCA concentration increased approximately 2-fold after irradiation but stayed to the baseline level after MSC injection. We propose from our observations that, following irradiation, MSC infusion indirectly corrected liver dysfunction by preventing gut damage. This explanation would be consistent with the absence of MSC engraftment in liver. These results evidenced that MSC treatment of a target organ may have an effect on distant tissues. This observation comes in support to the interest for the use of MSC for cellular therapy in multiple pathologies proposed in the recent years.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"2 1","pages":"45-50"},"PeriodicalIF":0.0,"publicationDate":"2009-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Injection of HGF Plasmid cDNA to Prevent Manifestation of Parkinson Disease: A Preclinical Study using a Primate Model 注射HGF质粒cDNA预防帕金森病表现:灵长类动物模型的临床前研究

The open gene therapy journal Pub Date : 2009-07-23 DOI: 10.2174/1875037000902010038

H. Koike, A. Ishida, Takuya Hayashi, M. Shimamura, S. Mizuno, Toshikazu Nakamura, H. Iida, T. Ogihara, Y. Kaneda, R. Morishita

{"title":"Injection of HGF Plasmid cDNA to Prevent Manifestation of Parkinson Disease: A Preclinical Study using a Primate Model","authors":"H. Koike, A. Ishida, Takuya Hayashi, M. Shimamura, S. Mizuno, Toshikazu Nakamura, H. Iida, T. Ogihara, Y. Kaneda, R. Morishita","doi":"10.2174/1875037000902010038","DOIUrl":"https://doi.org/10.2174/1875037000902010038","url":null,"abstract":"Parkinson disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Current therapies provide symptomatic treatment only and thus fail to prevent the process of neurodegeneration. Recently, it has been reported that neurotrophic factors could support the survival and enhance the function of dopaminergic neurons. Thus, gene therapy using neurotrophic factors has become the center of interest. From this viewpoint, we focused on hepatocyte growth factor (HGF) as a novel neurotrophic and angiogenic growth factor. In this study, we examined the effects of over-expression of HGF on clinical symptoms induced in a monkey model of PD, aiming toward human gene therapy. Stereotaxic transfection of naked plasmid DNA encoding human HGF cDNA into the striatum resulted in significant prevention of behavioral, immunohistochemical, HPLC and PET scan findings. Overall, the present study demonstrated that over-expression of HGF prevented neuronal death in a PD primate model, providing a potential novel therapy for PD.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"66 1","pages":"38-44"},"PeriodicalIF":0.0,"publicationDate":"2009-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Bcl-2 Over-Expression and Genetic Manipulation of T Cells Provides Tumor Specificity and Enhanced Resistance to Apoptosis In Vitro T细胞Bcl-2过表达和基因操作提供肿瘤特异性和增强细胞凋亡抗性

The open gene therapy journal Pub Date : 2009-06-08 DOI: 10.2174/1875037000902010029

H. Pegram, P. Darcy, M. Kershaw

引用次数: 0

Comparison between cationic polymer and lipid in plasmidic DNA delivery to the cell nucleus 质粒DNA向细胞核传递过程中阳离子聚合物与脂质的比较

The open gene therapy journal Pub Date : 2009-04-01 DOI: 10.2174/1875037000902010021

M. Conese, A. Biffi, G. Dina, N. Marziliano, A. Villa

引用次数: 6

Assessment of Genetic Shielding for Adenovirus Vectors 腺病毒载体遗传屏蔽的评价

The open gene therapy journal Pub Date : 2009-01-22 DOI: 10.2174/1875037000902010001

S. Hedley, Aleksandr Krendelshchikov, Myunghee Kim, Jian Chen, H. Hsu, J. Mountz, D. Curiel, I. Kovesdi

{"title":"Assessment of Genetic Shielding for Adenovirus Vectors","authors":"S. Hedley, Aleksandr Krendelshchikov, Myunghee Kim, Jian Chen, H. Hsu, J. Mountz, D. Curiel, I. Kovesdi","doi":"10.2174/1875037000902010001","DOIUrl":"https://doi.org/10.2174/1875037000902010001","url":null,"abstract":"Development of adenovirus (Ad) vectors in the clinical context has highlighted that vector efficacy may be limited by the host humoral response due to pre-existing titers of neutralizing antibodies against the vector itself in humans. Further, multiple dosing of Ad vectors based on serotype 5 would be limited. Current immune evasion strategies being investigated by other laboratories are only applicable to non-replicating vectors. Therefore we have proposed ge- netic shielding as an alternate that would be applicable to both non-replicating and conditionally replicating Ad vectors. Genetic shielding would encapsulate fusion of a self-protein to Ad minor capsid protein, pIX, as a means to cloak immu- nogenic capsid epitopes and prevent neutralization of Ad vectors through Ad specific antibodies. In the development of a suitably shielded Ad vector we choose several self-proteins that we attempted to fuse to pIX. We have also used an indirect method to conjugate albumin to the capsid through an albumin binding domain fused to pIX. Despite attaining novel pIX modified Ad vectors we found that none of the pIX attached molecules in this study prevented neutralizing an- tibodies from halting gene transfer.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"2 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2009-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

In Vivo Evidence of Enhancement of HGF-induced Angiogenesis by Fluvastatin 氟伐他汀增强hgf诱导的血管生成的体内证据

The open gene therapy journal Pub Date : 2008-06-05 DOI: 10.2174/1875037000801010001

Y. Takeya, H. Makino, M. Aoki, T. Miyake, K. Ozaki, H. Rakugi, T. Ogihara, R. Morishita

{"title":"In Vivo Evidence of Enhancement of HGF-induced Angiogenesis by Fluvastatin","authors":"Y. Takeya, H. Makino, M. Aoki, T. Miyake, K. Ozaki, H. Rakugi, T. Ogihara, R. Morishita","doi":"10.2174/1875037000801010001","DOIUrl":"https://doi.org/10.2174/1875037000801010001","url":null,"abstract":"Currently, therapeutic angiogenesis using gene transfer of angiogenic growth factors has entered the realm of novel therapy for patients with critical limb ischemia. However, its clinical utility might be enhanced by combination with classical pharmacological approaches. Thus, in this study, we examined adjunctive therapy to enhance the angiogenic ef- fects of gene transfer, with HMG-CoA reductase inhibitors, statins, which have pleiotropic vascular-protective effects. Here, we evaluated the effects of a combination of hepatocyte growth factor (HGF) gene therapy with fluvastatin in a mouse hindlimb ischemia model. Hindlimb ischemia model mice were given a normal diet, high-cholesterol diet (HCD) or HCD with fluvastatin, after in- tramuscular injection of human HGF plasmid DNA. Intramuscular injection of HGF plasmid into ischemic limbs signifi- cantly increased blood flow and capillary density. However, HCD diminished the increase in blood flow and capillary density induced by HGF gene transfer. Administration of fluvastatin significantly attenuated the reduction in blood flow and decrease in capillary density, while it did not change the serum cholesterol level. Overall, these results demonstrated that fluvastatin significantly enhanced the increase in blood flow and capillary density induced by HGF gene transfer in a hindlimb ischemia mouse model with HCD, through a non-cholesterol-lowering effect. Clinical use of fluvastatin might be possible adjunctive therapy to enhance therapeutic angiogenesis.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"1 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2008-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Enhanced Gene Delivery to Human Primary Endothelial Cells Using Tropism-Modified Adenovirus Vectors. 利用嗜性修饰的腺病毒载体增强人原代内皮细胞的基因传递。

The open gene therapy journal Pub Date : 2008-01-01 DOI: 10.2174/1875037000801010007

Meredith A Preuss, Joel N Glasgow, Maaike Everts, Mariam A Stoff-Khalili, Hongju Wu, David T Curiel

{"title":"Enhanced Gene Delivery to Human Primary Endothelial Cells Using Tropism-Modified Adenovirus Vectors.","authors":"Meredith A Preuss, Joel N Glasgow, Maaike Everts, Mariam A Stoff-Khalili, Hongju Wu, David T Curiel","doi":"10.2174/1875037000801010007","DOIUrl":"https://doi.org/10.2174/1875037000801010007","url":null,"abstract":"<p><p>Endothelial cells have been noted to have relatively low expression of the native receptor for adenovirus serotype 5 (Ad5), coxsackie and adenovirus receptor (CAR), and are thus refractory to Ad5 infection. In this study, we hypothesize that increases in the infectivity of Ad5 in primary human pulmonary artery (HPAEC), coronary artery (HCAEC) and umbilical vein endothelial cells (HUVEC) can be achieved through genetic capsid modification of Ad5 to bypass CAR-dependent infection. The modifications tested in this study include incorporation of an integrin-binding RGD peptide motif (Ad5.RGD), a poly-lysine motif (Ad5.pK7), a combination of both of these peptide domains (Ad5.RGD.pK7), an adenovirus serotype 3 knob domain (Ad5/3Luc1) and canine adenovirus serotype 1 or 2 knob domains (Ad5Luc1-CK1 and Ad5Luc1-CK2). In HPAEC and HCAEC, the greatest infectivity enhancements were achieved using Ad5/3Luc1 (26-fold and 30-fold respectively). HUVEC was most readily infected by Ad5Luc1-CK1 (213-fold). These results demonstrate that gains in Ad5 infectivity in endothelial cells can be accomplished with genetic capsid modifications.</p>","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"1 ","pages":"7-11"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761693/pdf/nihms106345.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28442748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14