Retrovirus-Mediated Gene Transfer into Salivary Glands<i>In Vivo</i>

Barka, Tibor; Noen, H M van der

doi:10.1089/hum.1996.7.5-613

Cited by 39 publications

(29 citation statements)

References 28 publications

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“…We have shown previously (Barka and van der Noen 1996) that rat submandibular gland-derived A5 cells can be infected and transduced by the retroviral vector BAG, which codes for bacterial ␤-galactosidase. A5 cells were also transduced by the retroviral vector DAP, which is structurally similar to BAG but codes for, in addition to the neomycin resistance gene, human placental alkaline phosphatase (Fields-Berry et al 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Before gene transfer to the SG in vivo, we performed in vitro experiments using the retroviral vector DAP and the A5 cell line. This cell line, established from the submandibular glands of weanling Fischer 344 rats , has been used in previous gene transfer experiments (Mastrangeli et al 1994;Barka and van der Noen 1996). The objectives were to establish that (a) salivary gland-derived cells can be infected by the DAP vector, (b) the transduced cells express PLAP encoded by the viral DNA, (c) the PLAP is membrane-bound, and (d) the transduced cells release AP into the culture medium.…”

Section: Retrovirus-mediated Gene Transfer and Expression Of Transducmentioning

confidence: 99%

“…Our previous work (Barka and van der Noen 1996) has established that retrograde duct injection of a retroviral vector is an effective means of gene transfer to the acinar cells of the SG in vivo, resulting in integration and long-term expression of the genes encoded by the vector. One of the limitations to the use of retroviral vectors, the requirement for cell division for integration of the viral DNA, was overcome by induction of cell division of acinar cells by administration of the ␤-adrenergic drug isoproterenol.…”

Section: Figure 17mentioning

confidence: 99%

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Retrovirus-mediated Gene Transfer into Rat Salivary Gland Cells In Vitro and In Vivo

Barka

Noen

1997

J Histochem Cytochem.

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SUMMARY A retroviral vector DAP that encodes the human placental alkaline phosphatase (PLAP) and the neomycin-resistant gene was used to transduce the salivary glandderived cell line A5 in vitro and acinar cells in rat submandibular gland in vivo. Expression of the transduced PLAP gene was established by histochemical staining for heat-resistant AP and by determination of enzyme activity. From the in vitro experiments, we concluded that the salivary gland-derived cell line A5 can be infected by the retroviral vector DAP. In the transduced cells the viral long terminal repeat (LTR) promoter was effective, and the cells expressed heat-stable PLAP which was localized mostly in the plasma membrane and could be released by treatment with bromelain or phosphatidyinositol-specific phospholipase C. A5-DAP cells secreted PLAP into the medium. Clones of A5-DAP cells expressed various levels of the enzyme. The level of enzyme activity in different clones was unrelated to growth rate. Retrograde ductal injection of the viral vector into the duct of the submandibular gland of rats resulted in integration and long-term expression of PLAP gene in acinar cells. Expression of PLAP was seen up to 25 days, the limit of the observation period. To facilitate integration of the viral DNA, cell division of acinar cells was induced by administration of the ␤ -adrenergic agonist isoproterenol before administration of the virus. PLAP was secreted into submandibular saliva. The data support the notion that salivary glands are suitable targets for gene transfer in vivo by a retroviral vector.

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Section: Discussionmentioning

confidence: 99%

Section: Retrovirus-mediated Gene Transfer and Expression Of Transducmentioning

confidence: 99%

Section: Figure 17mentioning

confidence: 99%

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Retrovirus-mediated Gene Transfer into Rat Salivary Gland Cells In Vitro and In Vivo

Barka

Noen

1997

J Histochem Cytochem.

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“…First, EAT-DAP cells producing the tumors were polyclonal, and it is known that cells transduced by retroviral vector DAP or BAG, the latter coding for bacterial ß-galactosidase, are heterogenous with respect to the expression of the transgene [15,20]. Such a heterogeneity exists even among cloned cells.…”

Section: Discussionmentioning

confidence: 99%

Passive Immunotherapy of Mice Bearing Ehrlich Ascites Tumor Expressing Human, Membrane-Bound Placental Alkaline Phosphatase

Barka

Henderson

Noen³

2000

Tumor Biol

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The objective of our study was to test if a tumor expressing a transgene coding for a membrane-bound protein is amenable to immunotherapy by antibodies to the same protein. To this end, we have established an Ehrlich ascites tumor (EAT) cell line, EAT-DAP, stably expressing human, membrane-bound placental alkaline phosphatase (PLAP) by infecting EAT cells (EATC) with the retroviral vector DAP and selecting neomycin-resistant cells. EATC and EAT-DAP cells grew at similar rates in vitro, and produced ascites tumor in Swiss-Webster mice with similar efficiency. We have treated mice bearing EAT-DAP ascites tumor with a mouse monoclonal antibody to human PLAP or with a monoclonal antibody to human C proteins of the heterogenous ribonucleoprotein complex (hnRNP). The average survival of mice treated with anti-hnRNP was 16.4 ± 1.1 days (n = 8). Treatment with anti-PLAP prolonged the survival of mice; in 4 mice average survival was 23.3 ± 5.7 days. Four animals, however, survived for 60 days when they were killed and had no visible signs of tumor. These data support the notion that passive immunotherapy using antibodies against a membrane protein, expressed in tumor cells transduced by a viral vector coding for that protein, may be effective in controlling tumor growth.

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“…Not surprisingly, some vectors are much better than others. For example, the commonly used retroviral vector, Moloney murine leukemia virus (MoMLV), which has been used for many clinical gene transfer protocols (e.g., Cavazzana-Calvo et al, 2000), is not very useful with salivary glands (Barka and Van der Noen, 1996;Shai et al, 2002). MoMLV vectors require cell division for successful transduction and salivary epithelial cells divide slowly, approximately every 180-240 days.…”

Section: Gene Transfer To Salivary Glandsmentioning

confidence: 99%

Utilizing endocrine secretory pathways in salivary glands for systemic gene therapeutics

Voutetakis

Wang

Baum

2003

Journal Cellular Physiology

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Mammalian salivary glands are commonly used models of exocrine secretion. However, there is substantial experimental evidence showing the physiological existence of endocrine secretory pathways in these tissues. The use of gene transfer technology in vivo has allowed the unambiguous demonstration of these endocrine pathways. We and others have exploited such findings and evaluated salivary glands as possible target tissues for systemic applications of gene therapeutics. Salivary glands present numerous advantages for this purpose, including being well encapsulated, which limits extra-glandular vector dissemination, and having the luminal membranes of almost all parenchymal cells accessible via intraoral delivery of vectors through the main excretory ducts. Existing studies suggest that clinical benefits will result from salivary gland targeted systemic gene therapeutics.

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Retrovirus-Mediated Gene Transfer into Salivary GlandsIn Vivo

Cited by 39 publications

References 28 publications

Retrovirus-mediated Gene Transfer into Rat Salivary Gland Cells In Vitro and In Vivo

Retrovirus-mediated Gene Transfer into Rat Salivary Gland Cells In Vitro and In Vivo

Passive Immunotherapy of Mice Bearing Ehrlich Ascites Tumor Expressing Human, Membrane-Bound Placental Alkaline Phosphatase

Utilizing endocrine secretory pathways in salivary glands for systemic gene therapeutics

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