Retroviral membrane display of apoptotic effector molecules

Strehlow, David; Jodo, Satoshi; Ju, Shyr‐Te

doi:10.1073/pnas.070049197

Cited by 16 publications

(22 citation statements)

References 25 publications

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“…BJAB-FADD-DN cells with a defect in death receptor signaling were not susceptible to LV.TRAIL-induced apoptosis, as expected. Previous reports have described the carryover of proteins expressed in producer cells by enveloped viral particles, 19 causing transduction-independent induction of apoptosis. To investigate the possibility of partial apoptosis induction by LV.TRAIL-particles containing TRAIL protein, we performed immunoprecipitation analysis of LV.GFP and LV.TRAIL using a TRAIL-specific antibody (1d).…”

Section: Production Of Lvtrail and Transduction Of Human Tumor Cell mentioning

confidence: 99%

Specific resistance upon lentiviral TRAIL transfer by intracellular retention of TRAIL receptors

et al. 2006

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in many transformed cells, suggesting TRAIL as an ideal candidate for cancer gene therapy. A main obstacle in cancer therapy is intrinsic or acquired therapy resistance of malignant cells. To study induction of resistance against TRAIL, we generated lentiviral vectors allowing efficient TRAIL expression and apoptosis induction in a variety of human cancer cell lines. Within days upon TRAIL overexpression, cells became resistant towards TRAIL, but not to CD95 ligation or DNA damage by cisplatin.

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Section: Production Of Lvtrail and Transduction Of Human Tumor Cell mentioning

confidence: 99%

Specific resistance upon lentiviral TRAIL transfer by intracellular retention of TRAIL receptors

et al. 2006

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“…This is in line with previous observations demonstrating that enveloped viruses with CD95-L or TRAIL transgenes carry these proteins on their surface, as a result from protein expression in the packaging cells. 24,37 Unfortunately, our attempt to further characterize this transduction-independent induction of cell death by AZT, an inhibitor of reverse transcriptase, was hampered, as this substance sensitizes for TRAIL-induced apoptosis (own observation, compare also Ghosh et al 32 ). Also, cells treated with AZT or ddC at concentrations required for inhibition of transduction underwent growth arrest after 5-7 days of culture (own data, not shown).…”

Section: Discussionmentioning

confidence: 99%

Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects

Wenger

Mattern²,

Haas

et al. 2006

Cancer Gene Ther

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, which selectively induces apoptosis in many transformed cells without apparent toxic side effects in normal tissue. We recently described the construction and characterization of a lentiviral vector for expression of TRAIL. In this report, we evaluate its suitability for therapeutic application. In vitro, we observed specific induction of apoptosis upon transduction in human lung cancer cells. Cell death was partially dependent on successful integration and TRAIL expression by the vectors, but was to some extent mediated by protein carryover, as we found TRAIL protein associated with virus particles. Transduction of subcutaneously growing lung tumors on nude mice with lentiviral TRAIL mediated a transient suppression of tumor growth. Analysis of tumor sections revealed that transduction efficiency of lentiviral control vector but not of lentiviral TRAIL vector was high. This was because of the direct cytotoxic activity of recombinant TRAIL present in viral particles, which prevented efficient tumor transduction. These data therefore suggest that enveloped viral vectors constitutively expressing TRAIL are well suited for ex vivo applications, such as the transduction of tumorhoming cells, but may have a lower effect when used directly for the transduction of tumor cells in vivo.

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“…Western blot analysis was conducted as previously described (9). Protein concentrations loaded were 0.1-5 g. For samples lacking detectable FasL, 5 g of total protein was loaded.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Cells at ϳ80% confluence were maintained in 150 mm ϫ 25 mm petri dishes in 25 ml of culture medium for 48 h. FasL VP and sFasL were prepared as previously described (9,10).…”

Section: Preparation Of Sfasl and Fasl Vpmentioning

confidence: 99%

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Cutting Edge: Fas Ligand (CD178) Cytoplasmic Tail Is a Positive Regulator of Fas Ligand-Mediated Cytotoxicity

Jodo

Pidiyar

Xiao

et al. 2005

The Journal of Immunology

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The cytotoxic function of CD178 (Fas ligand (FasL)) is critical to the maintenance of peripheral tolerance and immune-mediated tissue pathology. The active site of FasL resides at the FasL extracellular region (FasLExt) and it functions through binding/cross-linking Fas receptor on target cells. In this study, we report that FasLExt-mediated cytotoxicity is regulated by the FasL cytoplasmic tail (FasLCyt). Deleting the N-terminal 2–70 aa (Δ70) or N-terminal 2–33 aa (Δ33) reduced the cytotoxic strength as much as 30- to 100-fold. By contrast, change in the cytotoxic strength was not observed with FasL deleted of the proline-rich domains (45–74 aa, ΔPRD) in the FasLCyt. Our study identifies a novel function of FasLCyt and demonstrates that FasL2–33, a sequence unique to FasL, is critically required for the optimal expression of FasLExt-mediated cytotoxicity.

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Retroviral membrane display of apoptotic effector molecules

Cited by 16 publications

References 25 publications

Specific resistance upon lentiviral TRAIL transfer by intracellular retention of TRAIL receptors

Specific resistance upon lentiviral TRAIL transfer by intracellular retention of TRAIL receptors

Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects

Cutting Edge: Fas Ligand (CD178) Cytoplasmic Tail Is a Positive Regulator of Fas Ligand-Mediated Cytotoxicity

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