The open gene therapy journal最新文献

Using Electroporation to Determine Function of a Chimeric Antigen Receptor in T Cell and Macrophage Cell Lines 电穿孔法测定T细胞和巨噬细胞嵌合抗原受体的功能

The open gene therapy journal Pub Date : 2013-08-23 DOI: 10.2174/1875037020130715001

C. Yong, Connie P. M. Duong, Christel Devaud, Liza B. John, P. Darcy, M. Kershaw

{"title":"Using Electroporation to Determine Function of a Chimeric Antigen Receptor in T Cell and Macrophage Cell Lines","authors":"C. Yong, Connie P. M. Duong, Christel Devaud, Liza B. John, P. Darcy, M. Kershaw","doi":"10.2174/1875037020130715001","DOIUrl":"https://doi.org/10.2174/1875037020130715001","url":null,"abstract":"Chimeric antigen receptors (CARs) have been used extensively in adoptive immunotherapy to modify T lym- phocytes (CTLs), conferring the effector abilities of these cells towards a tumor-associated antigen (TAA). However, the ability of a CAR to redirect the effector function in a range of immune cells has not been well characterized, mainly due to the limitations in current genetic modification techniques. To overcome these limitations, we used the rapid technique of electroporation to transiently modify a macrophage, CD4 + T and CD8 + T cell line to express a CAR. This CAR consisted of an anti-ErbB2 extracellular single chain variable fragment region linked to the intracellular signaling domain compris- ing CD28-CD3ζ. The ability of three different promoters (CMV, Vav and LTR) to drive CAR expression was compared within each of the cell lines. CAR expression was highest under the CMV promoter in all cell lines, with expression rang- ing from 20-80%. We subsequently performed functional analysis of these CMV-CAR expressing cells, and observed an- tigen-specific release of IFN-γ from the CD8 + and CD4 + T cell lines. In addition, antigen-specific release of both IL-2 and IL-17 was also detected from the CD4 + T cell line, EL4. Overall this investigation demonstrated the feasibility of elec- troporation to compare promoter activity, induce rapid expression and subsequent function of a CAR in a number of he- matopoietic cell lines.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"5 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2013-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107777","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: 1

Controlling Adenoviral Replication to Induce Oncolytic Efficacy 控制腺病毒复制诱导溶瘤效果

The open gene therapy journal Pub Date : 2013-07-02 DOI: 10.2174/1875037001003010015

C. Fillat, Anabel José, X. B. Ros, A. Mato-Berciano, M. V. Maliandi, D. Abate-Daga

引用次数: 4

Adenovirus Release from the Infected Cell as a Key Factor for Adenovirus Oncolysis 腺病毒从感染细胞中释放是腺病毒溶瘤的关键因素

The open gene therapy journal Pub Date : 2013-07-02 DOI: 10.2174/1875037001003010024

A. Gros, S. Guedan

引用次数: 12

Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response 靶向腺病毒进入增强溶瘤抗肿瘤反应

The open gene therapy journal Pub Date : 2013-07-02 DOI: 10.2174/1875037001003010009

H. Haisma, Lieke Geerts

{"title":"Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response","authors":"H. Haisma, Lieke Geerts","doi":"10.2174/1875037001003010009","DOIUrl":"https://doi.org/10.2174/1875037001003010009","url":null,"abstract":"Conditionally replicative adenoviruses represent an innovative group of anticancer agents designed to destroy these cells by replication and lysis. A major problem associated with of the use of adenoviral vectors in gene therapy is its high liver uptake and lack of tumor selectivity upon systemic administration. To improve the efficacy of CRAds as anticancer agents, their infection efficiency on CAR-deficient tumor cells could be enhanced their by redirecting viral entry via a CAR-independent pathway. To redirect the entry pathway of adenoviruses and enhance their infectivity and specificity, two general strategies are being used. In the first strategy, the adenovirus genome is changed to alter the binding specificity of the viral capsid. In the second strategy, a two-component targeted adenovirus is created by binding of proteins with specific affinity for cancer cells onto the viral capsid. Despite effective targeting and tumor eradication in vitro and in mouse models, the results from systemic administration of targeted CrAds is limited. In addition, clinical effects of CrAds are disappointing up till now. Therefore, combination therapies in which targeted CrAds are combined with other types of therapy are being investigated.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"3 1","pages":"9-14"},"PeriodicalIF":0.0,"publicationDate":"2013-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107825","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: 1

Editorial - Advances in Oncolytic Antitumour Adenoviral Therapies: Three Key Aspects 社论-溶瘤性抗肿瘤腺病毒治疗的进展:三个关键方面

The open gene therapy journal Pub Date : 2013-07-02 DOI: 10.2174/1875037001003010008

C. Fillat

{"title":"Editorial - Advances in Oncolytic Antitumour Adenoviral Therapies: Three Key Aspects","authors":"C. Fillat","doi":"10.2174/1875037001003010008","DOIUrl":"https://doi.org/10.2174/1875037001003010008","url":null,"abstract":"Oncolytic virotherapy based on adenoviral vectors is an intensive area of research and many advances are being conducted with the general aim to come up with full potential oncolytic adenoviruses to be effective in the human clinical context. Two main concepts are driving the genetic engineering of adenoviruses. On one hand there are the strategies directed towards enhancing the viral potency and on the other those that focus on adenoviral selectivity. This special issue reviews current research on adenoviral oncolysis by focusing on three key aspects in adenoviral biology: viral entrance to the cell, viral replication, and viral exit from the cell. The first review \" Targeting adenoviral entry to enhance oncolytic antitumor response \" discusses on the effectiveness of pseudotyping, genetic targeting or the use of adaptor molecules to enter adenovirus into tumor cells. It also summarizes the effects of detargeting adenovirus from their natural tropism, of special interest in systemic applications to treat disseminated disease. The second review \" Controlling adenoviral replication to induce oncolytic efficacy \" discusses on the broad number of genetic elements that are being engineer into the adenoviral genome to control replication. And how the increased knowledge on the specific behavior and regulation of neoplastic cells and tumor microenvironment can be exploited to develop novel oncolytic adenoviruses. The third review \" Adenovirus release from the infected cell as a key factor for adenoviral oncolysis \" summarizes the strategies used to facilitate adenoviral spreading into the tumor by favoring the release from the infected cells. In a first term it reviews the biology of adenoviral release. This special issue highlights the hot-topic aspects in the expanding field of adenoviral oncolysis where many new and exciting developments are rapidly being generated. which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"3 1","pages":"8-8"},"PeriodicalIF":0.0,"publicationDate":"2013-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107816","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

T cell receptor fused to CD3ζ: Transmembrane domain of CD3ζ prevents TCR mis-pairing, whereas complete CD3ζ directs functional TCR expression T细胞受体与CD3ζ融合:CD3ζ的跨膜结构域防止TCR错配，而完整的CD3ζ指导功能性TCR表达

The open gene therapy journal Pub Date : 2011-10-11 DOI: 10.2174/1875037001104010011

C. Govers, Z. Sebestyén, C. Berrevoets, H. Venselaar, R. Debets

{"title":"T cell receptor fused to CD3ζ: Transmembrane domain of CD3ζ prevents TCR mis-pairing, whereas complete CD3ζ directs functional TCR expression","authors":"C. Govers, Z. Sebestyén, C. Berrevoets, H. Venselaar, R. Debets","doi":"10.2174/1875037001104010011","DOIUrl":"https://doi.org/10.2174/1875037001104010011","url":null,"abstract":"textabstractTCR gene therapy represents a feasible and promising treatment for patients with cancer and virus infections. Currently, this treatment rationale is hampered by diluted surface expression of the TCR transgene and generation of potentially self reactive T-cells, both a direct consequence of mis-pairing with endogenous TCR chains. As we reported previously (Gene Ther 16:1369, 2000; J Immunol 180:7736, 2008), TCR mis-pairing can be successfully addressed by a TCR:CD3ζ fusion protein (i.e., TCR:ζ). Here, we set out to minimize the content of CD3ζ in TCR:ζ, specific for MAGEA1/ HLA-A1, without compromising TCR pairing and function. Domain-exchange and 3D-modeling strategies defined a set of minimal TCR:ζ variants, which, together with a murinized and cysteine-modified TCR (TCR:mu+cys), were tested for functional TCR expression and TCR pairing. Our data with Jurkat T cells show that the CD3ζ transmembrane domain is important for cell-surface expression, whereas the CD3ζ intracellular domain is crucial for T-cell activation. Notably, inability of TCR:ζ to mis-pair was not observed for TCR:mu+cys, which depended exclusively on the transmembrane domain of CD3ζ and could not be recapitulated by a limited number of structurally defined CD3ζ transmembrane amino acids. The extracellular CD3ζ domain was dispensable for TCR:ζ's ability to prevent TCR mis-pairing, bind pMHC and mediate NFAT activation. In primary human T cells, however, minimal TCR:ζ without CD3ζ's extracellular domain but not TCR:ζ nor TCR:mu+cys revealed compromised cell surface expression and T cell function. Taken together, our study demonstrates that CD3ζ's transmembrane domain dictates TCR:ζ's inability to TCR mis-pair, but only TCR coupled to complete CD3ζ and not its minimal variants were functionally expressed in primary T cells.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"4 1","pages":"11-22"},"PeriodicalIF":0.0,"publicationDate":"2011-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107772","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: 10

Ceiling Culture-Derived Proliferative Adipocytes are A Possible Delivery Vehicle for Enzyme Replacement Therapy in Lecithin: Cholesterol Acyltransferase Deficiency 天花板培养衍生的增生性脂肪细胞是卵磷脂:胆固醇酰基转移酶缺乏症的酶替代治疗的可能递送载体

The open gene therapy journal Pub Date : 2011-03-15 DOI: 10.2174/1875037001104010001

Masayuki Kuroda, Y. Aoyagi, Sakiyo Asada, H. Bujo, Shigeaki Tanaka, T. Konno, M. Tanio, I. Ishii, K. Machida, F. Matsumoto, K. Satoh, Masayuki Aso, Y. Saito

{"title":"Ceiling Culture-Derived Proliferative Adipocytes are A Possible Delivery Vehicle for Enzyme Replacement Therapy in Lecithin: Cholesterol Acyltransferase Deficiency","authors":"Masayuki Kuroda, Y. Aoyagi, Sakiyo Asada, H. Bujo, Shigeaki Tanaka, T. Konno, M. Tanio, I. Ishii, K. Machida, F. Matsumoto, K. Satoh, Masayuki Aso, Y. Saito","doi":"10.2174/1875037001104010001","DOIUrl":"https://doi.org/10.2174/1875037001104010001","url":null,"abstract":"Human proliferative adipocytes propagated via ceiling culture technique from subcutaneous fat tissue (desig- nated as ccdPA) were herein evaluated for their potential as a recipient for retroviral vector-mediated gene transduction of a therapeutic protein delivery. Exposure to the ZsGreen-expressing vector supernatant using a cell preparation generated by a 7-day ceiling culture induced a 40-50% transduction efficiency, with less than two integrated copies of viral genome per cell on average. The lcat gene-transduced human ccdPA secreted functional LCAT protein, correlating with the inte- grated copy number of vector genome. The gene-transduced cells could be expanded up to nearly 10 12 cells from 1 g of fat tissue within one month after fat tissue preparation. The cells also maintained the potential to differentiate into adipocytes in vitro. The presence of human LCAT protein in serum was immunologically identified upon transplantation of lcat- expressing ccdPA into the adipose tissue of immune-deficient mice. These results indicated that human ccdPA has a novel therapeutic potential for LCAT-deficient patients. The clinical application in combination with cell transplantation shed a light on a development of a life-long protein replacement therapy for LCAT-deficient patients.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"4 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2011-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107763","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: 22

Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response~!2009-12-10~!2010-01-29~!2010-05-26~! 靶向腺病毒进入增强溶瘤抗肿瘤反应2009-12-10 2010-01-29 2010-05-26

The open gene therapy journal Pub Date : 2010-06-04 DOI: 10.2174/1875037001003020009

H. Haisma, Lieke Geerts

{"title":"Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response~!2009-12-10~!2010-01-29~!2010-05-26~!","authors":"H. Haisma, Lieke Geerts","doi":"10.2174/1875037001003020009","DOIUrl":"https://doi.org/10.2174/1875037001003020009","url":null,"abstract":"Conditionally replicative adenoviruses represent an innovative group of anticancer agents designed to destroy these cells by replication and lysis. A major problem associated with of the use of adenoviral vectors in gene therapy is its high liver uptake and lack of tumor selectivity upon systemic administration. To improve the efficacy of CRAds as anticancer agents, their infection efficiency on CAR-deficient tumor cells could be enhanced their by redirecting viral entry via a CAR-independent pathway. To redirect the entry pathway of adenoviruses and enhance their infectivity and specificity, two general strategies are being used. In the first strategy, the adenovirus genome is changed to alter the binding specificity of the viral capsid. In the second strategy, a two-component targeted adenovirus is created by binding of proteins with specific affinity for cancer cells onto the viral capsid. Despite effective targeting and tumor eradication in vitro and in mouse models, the results from systemic administration of targeted CrAds is limited. In addition, clinical effects of CrAds are disappointing up till now. Therefore, combination therapies in which targeted CrAds are combined with other types of therapy are being investigated.","PeriodicalId":88328,"journal":{"name":"The open gene therapy journal","volume":"3 1","pages":"9-14"},"PeriodicalIF":0.0,"publicationDate":"2010-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68107877","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: 1

Controlling Adenoviral Replication to Induce Oncolytic Efficacy~!2009-11-11~!2010-01-02~!2010-05-26~! 控制腺病毒复制诱导溶瘤效果2009-11-11 2010-01-02 2010-05-26

The open gene therapy journal Pub Date : 2010-06-04 DOI: 10.2174/1875037001003020015

C. Fillat, Anabel José, X. B. Ros, A. Mato-Berciano, M. V. Maliandi, D. Abate-Daga

引用次数: 4

Adenovirus Release from the Infected Cell as a Key Factor for Adenovirus Oncolysis~!2009-10-09~!2010-02-25~!2010-05-26~! 感染细胞释放腺病毒是腺病毒溶瘤的关键因素2010-10-09 2010-02-25 2010-05-26

The open gene therapy journal Pub Date : 2010-06-04 DOI: 10.2174/1875037001003020024

A. Gros, S. Guedan

引用次数: 10