Comparative transduction efficiencies of human and nonhuman adenoviral vectors in human, murine, bovine, and porcine cells in culture

Bangari, Dinesh S.; Shukla, Sudhanshu; Mittal, Suresh K.

doi:10.1016/j.bbrc.2004.12.099

Cited by 58 publications

(90 citation statements)

References 23 publications

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“…The reasons for the apparent lower susceptibility of HepG2 cells in vitro are not known. Both cell lines express the CAR receptor and high levels of hTERT mRNA, but Hep3B cells internalize adenoviral particles more efficiently than HepG2 cells (18)(19)(20). However, both cell lines are comparably efficient at transferring adenoviral DNA into the nucleus and replicating the viral genome (20).…”

Section: Resultsmentioning

confidence: 99%

Systemic Gene-Directed Enzyme Prodrug Therapy of Hepatocellular Carcinoma Using a Targeted Adenovirus Armed with Carboxypeptidase G2

et al. 2005

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Hepatocellular carcinoma is the fifth most common cancer worldwide, and there is no effective therapy for unresectable disease. We have developed a targeted systemic therapy for hepatocellular carcinoma. The gene for a foreign enzyme is selectively expressed in the tumor cells and a nontoxic prodrug is then given, which is activated to a potent cytotoxic drug by the tumor-localized enzyme. This approach is termed gene-directed enzyme prodrug therapy (GDEPT). Adenoviruses have been used to target cancer cells, have an intrinsic tropism for liver, and are efficient gene vectors. Oncolytic adenoviruses produce clinical benefits, particularly in combination with conventional anticancer agents and are well tolerated. We rationalized that such adenoviruses, if their expression were restricted to telomerase-positive cancer cells, would make excellent gene vectors for GDEPT therapy of hepatocellular carcinoma. Here we use an oncolytic adenovirus to deliver the prodrug-activating enzyme carboxypeptidase G2 (CPG2) to tumors in a single systemic administration. The adenovirus replicated and produced high levels of CPG2 in two different hepatocellular carcinoma xenografts (Hep3B and HepG2) but not other tissues. GDEPT enhanced the adenovirus-alone therapy to elicit tumor regressions in the hepatocellular carcinoma models. This is the first time that CPG2 has been targeted and expressed intracellularly to effect significant therapy, showing that the combined approach holds enormous potential as a tumor-selective therapy for the systemic treatment of hepatocellular carcinoma. (Cancer Res 2005; 65(12): 5003-8)

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Section: Resultsmentioning

confidence: 99%

Systemic Gene-Directed Enzyme Prodrug Therapy of Hepatocellular Carcinoma Using a Targeted Adenovirus Armed with Carboxypeptidase G2

et al. 2005

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“…Since it can be expected that any vaccine prime-boost combination containing rAd5 will be seriously inhibited, a novel Ad vector distinct from rAd35 and rAd5 is required. Such a vector could be generated from the pool of human Ads, provided that human serotypes with low seroprevalence are still available, or prime-boost combinations could be tested utilizing Ad vectors developed from nonhuman Ad serotypes such as bovine (2), canine (23), avian (26), or chimpanzee (13) vectors.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Protection of a Recombinant Human Adenovirus Serotype 35-Based Malaria Vaccine againstPlasmodium yoeliiin Mice

et al. 2006

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Given the promise of recombinant adenovirus type 5 (rAd5) as a malaria vaccine carrier in preclinical models, we evaluated the potency of rAd35 coding for Plasmodium yoelii circumsporozoite protein (rAd35PyCS). We chose rAd35 since a survey with serum samples from African subjects demonstrated that human Ad35 has a much lower seroprevalence of 20% and a much lower geometric mean neutralizing antibody titer (GMT) of 48 compared to Ad5 (seroprevalence, 85%; GMT, 1,261) in countries with a high malaria incidence. We also demonstrated that immunization with rAd35PyCS induced a dose-dependent and potent, CS-specific CD8 ؉ cellular and humoral immune response and conferred significant inhibition (92 to 94%) of liver infection upon high-dose sporozoite challenge. Furthermore, we showed that in mice carrying neutralizing antibody activity against Ad5, mimicking a human situation, CS-specific T-and B-cell responses were significantly dampened after rAd5PyCS vaccination, resulting in loss of inhibition of liver infection upon sporozoite challenge. In contrast, rAd35 vaccine was as potent in naive mice as in Ad5-preimmunized mice. Finally, we showed that heterologous rAd35-rAd5 prime-boost regimens were more potent than rAd35-rAd35 because of induction of anti-Ad35 antibodies after rAd35 priming. The latter data provide a further rationale for developing rAd prime-boost regimens but indicate that priming and boosting Ad vectors must be immunologically distinct and also should be distinct from Ad5. Collectively, the data presented warrant further development of rAd35-based vaccines against human malaria.

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“…While the first adenovirus studies were carried out with human serotype 5, and to a lesser extent human serotype 2, subsequent studies have led to identification of multiple adenovirus serotypes, both human and nonhuman (Dobbelstein, 2003;Bangari et al, 2005;Stone and Lieber, 2006). This led to the concept of ''seroswitch,'' that is, to circumvent the antiadenovirus immunity elicited by the initial administration of an adenovirus gene transfer vector by administering an adenovirus vector comprised of a different serotype carrying the same gene, a strategy that is effective in experimental animals (Mastrangeli et al, 1996;Mack et al, 1997).…”

Section: Adenovirus Gene Transfer Vectorsmentioning

confidence: 99%

Adenovirus: The First EffectiveIn VivoGene Delivery Vector

2014

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Comparative transduction efficiencies of human and nonhuman adenoviral vectors in human, murine, bovine, and porcine cells in culture

Cited by 58 publications

References 23 publications

Systemic Gene-Directed Enzyme Prodrug Therapy of Hepatocellular Carcinoma Using a Targeted Adenovirus Armed with Carboxypeptidase G2

Systemic Gene-Directed Enzyme Prodrug Therapy of Hepatocellular Carcinoma Using a Targeted Adenovirus Armed with Carboxypeptidase G2

Immunogenicity and Protection of a Recombinant Human Adenovirus Serotype 35-Based Malaria Vaccine againstPlasmodium yoeliiin Mice

Adenovirus: The First EffectiveIn VivoGene Delivery Vector

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