Engineered expression of the Coxsackie B and adenovirus receptor (CAR) in human dendritic cells enhances recombinant adenovirus-mediated gene transfer

Stockwin, Luke H.; Matzow, Torkjel; Georgopoulos, Nikolaos T.; Stanbridge, Lindsay J.; Jones, Samantha V; Martin, I. G.; Blair-Zajdel, Maria E; Blair, G. Eric

doi:10.1016/s0022-1759(01)00510-5

Cited by 21 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8). In line with previous reports of the poor expression of CAR (2,37,38) and elevated levels of CD40 in DC (6,7), the use of the Ad5 fiber knob and scFv G28.5 as inhibitors of infection revealed that the CD40-mediated component of overall gene transfer by the targeted vectors was higher than that involving CAR, which was observed for untargeted Ad. On another note, the scFv G28.5 constituent of the targeting protein was more efficient in directing the vector complex to DCs than was the natural ligand of CD40, CD40L, thus further supporting the choice of scFvs as targeting moieties for Ad.…”

Section: Vol 77 2003 Ad Vectors Modified With Staphylococcus Proteisupporting

confidence: 89%

Targeting ofAdenovirus via Genetic Modification of the Viral Capsid Combined with aProteinBridge

Korokhov

Mikheeva

Krendelshchikov

et al. 2003

J Virol

View full text Add to dashboard Cite

Section: Vol 77 2003 Ad Vectors Modified With Staphylococcus Proteisupporting

confidence: 89%

Targeting ofAdenovirus via Genetic Modification of the Viral Capsid Combined with aProteinBridge

Korokhov

Mikheeva

Krendelshchikov

et al. 2003

J Virol

View full text Add to dashboard Cite

“…Although we were unable to examine the expression of CAR on the surface of mBM-DCs, we surmised that expression was low because of the previously reported relation between the amount of CAR on the cell surface and mRNA expression levels. 36,37 In fact, although conventional Ad at an MOI of 100 exhibited only 35% of gene transduction efficiency in mBM-DCs, AdRGD markedly improved both transduction efficiency (2.4-fold higher) and expression intensity (7-fold higher) under the same infection conditions (Fig 2). Furthermore, AdRGD at an MOI of 10 unexpectedly delivered an equivalent amount of foreign gene into mBM-DCs as conventional Ad at an MOI of 100.…”

Section: Discussionmentioning

confidence: 90%

Gene transduction efficiency and maturation status in mouse bone marrow-derived dendritic cells infected with conventional or RGD fiber-mutant adenovirus vectors

et al. 2003

View full text Add to dashboard Cite

Since dendritic cells (DCs) play a critical role in establishing antigen-specific adaptive immune responses, in the past several years, therapeutic strategies using genetically modified DCs against cancer and infectious diseases have attracted increasing attention. In the present study, we demonstrated that RGD fiber-mutant adenovirus vector (AdRGD) exhibited markedly superior gene transduction efficiency in mouse bone marrow-derived DCs (mBM-DCs) compared to conventional adenovirus vector (Ad). Likewise, this vector exhibited superior major histocompatibility complex class I-restricted presentation of antigen derived from the delivered gene in mBM-DCs. In order to investigate the effect of Ad-infection on the DC-differentiation process (maturation), we used three types of AdRGD and three conventional Ad to transduce mBM-DCs. These vectors carried either no transgene, LacZ gene, or gp100 gene. Infection by any of the Ad vectors enhanced the expression of MHC class II molecules in mBM-DCs. CD80, CD86, and CD40 expression and IL-12 production were more efficient in AdRGD-infected mBM-DCs than in conventional Adinfected cells. Contrary to our expectations, endocytotic activity of mBM-DCs decreased only slightly upon Ad-infection, whereas antigen uptake by lipopolysaccharide (LPS)-driven mature mBM-DCs was significantly impaired. However, our reverse transcription-polymerase chain reaction analysis revealed that Ad-infection resulted in the upregulation of the chemokine receptor CCR7 and downregulation of CCR6 in mBM-DCs and LPS-stimulated cells. We, therefore, concluded that Ad-infection directly influenced DC-maturation, although the effects were milder than under LPS-stimulation. In addition, this change in the immunologic properties of DCs resulted primarily from an increase in the number of Ad-particles capable of invading the cells rather than from the expression of foreign genes. AdRGD-infection caused greater induction of maturation than conventional Adinfection, irrespective of the type of transgene inserted.

show abstract

“…43 Engineering overexpression of CAR in target cells that are physiologically CARnegative may improve their transduction. 44 Finally, the biodistribution of adenovirus vectors in the pancreas of the intact host requires further study. A recent study of mouse organs following intravenous administration of wild-type Ad5 has shown that the pancreas is targeted by Ad5 but levels of uptake are much lower than in liver, spleen or lung tissues, 45 suggesting that improvements to targeting of adenoviruses to the pancreas are needed for effective treatment of pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

The roles of cell surface attachment molecules and coagulation Factor X in adenovirus 5-mediated gene transfer in pancreatic cancer cells

et al. 2011

View full text Add to dashboard Cite

Transduction of 11 pancreatic cancer cell lines with a replication-deficient adenovirus 5 expressing enhanced green fluorescent protein (Ad5EGFP) was analyzed and variable EGFP levels were observed, ranging from o1% to B40% of cells transduced, depending on the cell line. Efficient Ad5EGFP transduction was associated mainly with higher levels of cell surface Coxsackie and adenovirus receptor (CAR) but not with expression of a v b 3 and a v b 5 integrins and was fiber dependent. Reduction of CAR by RNA interference resulted in a corresponding decrease in Ad5EGFP transduction. Pre-treatment of Ad5EGFP with blood coagulation Factor X increased virus entry even in the presence of low CAR levels generated by RNA interference, suggesting a potential alternative route of Ad5 entry into pancreatic cancer cells. Immunohistochemistry carried out on 188 pancreatic ductal adenocarcinomas and 68 matched controls showed that CAR was absent in 102 (54%) of adenocarcinomas, whereas moderate and strong staining was observed in 58 (31%) and 28 (15%) cases, respectively. Weak or absent CAR immunolabeling correlated with poor histological differentiation of pancreatic cancer. In normal tissue, strong immunolabeling was detected in islet cells and in the majority of inter-and intralobular pancreatic ducts.

show abstract

Engineered expression of the Coxsackie B and adenovirus receptor (CAR) in human dendritic cells enhances recombinant adenovirus-mediated gene transfer

Cited by 21 publications

References 27 publications

Targeting ofAdenovirus via Genetic Modification of the Viral Capsid Combined with aProteinBridge

Targeting ofAdenovirus via Genetic Modification of the Viral Capsid Combined with aProteinBridge

Gene transduction efficiency and maturation status in mouse bone marrow-derived dendritic cells infected with conventional or RGD fiber-mutant adenovirus vectors

The roles of cell surface attachment molecules and coagulation Factor X in adenovirus 5-mediated gene transfer in pancreatic cancer cells

Contact Info

Product

Resources

About