Tetracycline Repressor, tetR, rather than the tetR–Mammalian Cell Transcription Factor Fusion Derivatives, Regulates Inducible Gene Expression in Mammalian Cells

Yao, Feng; Svensjö, Tor; Winkler, Thomas; Lu, Michael L.; Eriksson, Carl; Eriksson, Elof

doi:10.1089/hum.1998.9.13-1939

Cited by 235 publications

(212 citation statements)

References 38 publications

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“…The replication-defective adenovirus vector Ad.VSV-G, which utilizes the tetracycline-inducible T-Rex expression system (42) to encode a codon optimized VSV-G, was described previously under the name Ad-VSV-G (43). The adenovirus vector Ad.IL-2 encoding human IL-2, which is cross-active in mice (44), was described previously (45 (46).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic immune response induced by intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus and cytokines encoded by adenoviral vectors

Hoffmann¹,

Bayer²,

Wildner

2007

Int J Mol Med

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Abstract.We assessed whether intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus (VSV-G), encoded by a replication-defective adenovirus vector (Ad.VSV-G), alone or in combination with local coexpression of cytokines induces tumor-specific immune responses in a syngeneic murine colon cancer model. We confirmed in vitro by dye colocalization that transduction of murine cells with Ad.VSV-G induces cell-cell fusion. In a bilateral syngeneic subcutaneous colon cancer model in C57BL/6 and BALB/c mice, we demonstrated that intratumoral injection of Ad.VSV-G leads to a significant growth reduction of the directly vector-treated tumor, but also of the contralateral not directly vector-treated tumor. When compared to monotherapy, the anti-neoplastic efficacy was significantly enhanced when intratumoral Ad.VSV-G administration was combined with adenovirus vectors encoding IL-2, IL-12, IL-18, IL-21, or GM-CSF. The antitumor effects of the first three cytokines in combination with VSV-G expression were somewhat greater than those of the latter two. However, the differences did not reach statistical significance. The combination therapy resulted also in a significantly enhanced survival when compared to monotherapy. In addition, we demonstrated that intratumoral expression of VSV-G in combination with the tested cytokines induced a strong tumor-specific cytotoxic T lymphocyte (CTL) response and infiltration of tumors with macrophages. The effects of the combination therapy were clearly greater than those of the monotherapy. Our experimental data indicate that intratumoral expression of VSV-G, particularly in combination with cytokines, is a promising novel tool for the development of in situ tumor vaccination approaches.

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Section: Methodsmentioning

confidence: 99%

Therapeutic immune response induced by intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus and cytokines encoded by adenoviral vectors

Hoffmann¹,

Bayer²,

Wildner

2007

Int J Mol Med

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“…Stable tetracycline-inducible RCEC lines expressing dominant negative (d/n)-Erk1 and d/ n-p38 were developed, as previously described (Yao et al, 1998), and maintained in the culture medium described above but without gentamicin. Expression of d/n-Erk1 and d/n-p38 was elicited using 1 μg/ml tetracycline (Sigma, St. Louis, MO, USA) for 24 h.…”

Section: Cell Culturementioning

confidence: 99%

Differential dependence of regulatory volume decrease behavior in rabbit corneal epithelial cells on MAPK superfamily activation

Pan¹,

Capó-Aponte²,

Zhang³

et al. 2007

Experimental Eye Research

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We characterized the dependence of hypotonicity-induced regulatory volume decrease (RVD) responses on mitogen-activated protein kinase (MAPK) pathway signaling in SV40-immortalized rabbit corneal epithelial cells (RCEC). Following calcein-AM loading, RVD was monitored using a microplate fluorescence reader. Western blot analysis determined MAPK activation. After 30 min, the RVD response restored the relative cell volume to nearly isotonic values, whereas it was inhibited when cells were bathed either in a Cl − -free solution or with the Cl − -channel inhibitors: 5-nitro-2-(3-phenylpropylamino) benzoic acid or niflumic acid. Similar declines occurred with either a high-K + (20 mM) supplemented solution or the K + channel inhibitor 4-aminopyridine. Activation of extracellular signal-regulated kinase (ERK), p38, and stress-activated protein kinase/c-Jun Nterminal kinase (SAPK/JNK) was time and tonicity-dependent. Stimulation of ERK and SAPK/JNK was maximized earlier than that of p38. Activation of ERK and SAPK/JNK was insensitive to Cl − and K + channel inhibitors, whereas inhibition with either PD98059 or SP600125, respectively, blocked RVD. However, inhibition of p38 with SB203580 had no effect on RVD. Suppression of RVD instead blocked p38 activation. Differences in the dependence of RVD activation on Erk1/2 and p38 signaling were validated in dominant negative (d/n) -Erk1 and d/n-p38 cells. Volumesensitive Cl − and K + channel activation contributes, in concert, to RVD in RCEC. Therefore, swelling-induced ERK and SAPK/JNK stimulation precedes Cl − and K + channel activation, whereas p38 activation occurs as a consequence of RVD.

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“…U2OS cells express a cellular activity that can substitute functionally for HSV-1 regulatory protein ICP0 (59). U2CEP4R11 cells, a tetR-expressing cell line derived from U2OS cells, were grown and maintained in the above-described growth medium in the presence of hygromycin B at a concentration of 50 g/ml (61).…”

Section: Cells and Virusesmentioning

confidence: 99%

The Dominant-Negative Herpes Simplex Virus Type 1 (HSV-1) Recombinant CJ83193 Can Serve as an Effective Vaccine against Wild-Type HSV-1 Infection in Mice

Augustinova

Hoeller

Yao

2004

J Virol

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By selectively regulating the expression of the trans-dominant-negative mutant polypeptide UL9-C535C, of herpes simplex virus type 1 (HSV-1) origin binding protein UL9 with the tetracycline repressor (tetR)-mediated gene switch, we recently generated a novel replication-defective and anti-HSV-specific HSV-1 recombinant, CJ83193. The UL9-C535C peptides expressed by CJ83193 can function as a potent intracellular therapy against its own replication, as well as the replication of wild-type HSV-1 and HSV-2 in coinfected cells. In this report, we demonstrate that CJ83193 cannot initiate acute productive infection in corneas of infected mice nor can it reactivate from trigeminal ganglia of mice latently infected by CJ83193 in a mouse ocular model. Given that CJ83193 is capable of expressing the viral ␣, ␤, and ␥1 genes but little or no ␥2 genes, we tested the vaccine potential of CJ83193 against HSV-1 infection in a mouse ocular model. Our studies showed that immunization with CJ83193 significantly reduced the yields of challenge HSV in the eyes and trigeminal ganglia on days 3, 5, and 7 postchallenge. Like in mice immunized with the wild-type HSV-1 strain KOS, immunization of mice with CJ83193 prevents the development of keratitis and encephalitis induced by corneal challenge with wild-type HSV-1 strain mP. Delayed-type hypersensitivity (DTH) assays demonstrate that CJ83193 can elicit durable cell-mediated immunity at the same level as that of wild-type HSV-1 and is more effective than that induced by d27, an HSV-1 ICP27 deletion mutant. Moreover, mice immunized with CJ83193 developed strong, durable HSV-1-neutralizing antibodies at levels at least twofold higher than those induced by d27. The results presented in this report have shed new light on the development of effective HSV viral vaccines that encode a unique safety mechanism capable of inhibiting the mutant's own replication and that of wild-type virus.Herpesviruses can cause both an acute productive infection and a long-term latent infection characterized by periodic recurrences (54). Among the human herpesviruses, herpes simplex virus types 1 and type 2 (HSV-1 and -2, respectively) are most closely related and share significant DNA sequence homology (15,31,32). Although HSV infections are often asymptomatic, their clinical manifestations include oral-facial infections, genital herpes, neonatal herpes, keratoconjunctivitis, and herpes encephalitis (48,54). Despite the availability of various effective antiviral therapies, the spread of genital herpes infection continues to increase worldwide and has increased by 30% in the United States in the past two decades (19). The failure of antiviral therapy in effectively controlling the spread of HSV disease and the life-long nature of the infection present a strong need for developing safe and efficacious vaccines against HSV infections (48, 54).HSV replicates in epithelial cells and establishes life-long latent infection in neuronal cell bodies within the sensory ganglia of infected individuals. During productive i...

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Tetracycline Repressor, tetR, rather than the tetR–Mammalian Cell Transcription Factor Fusion Derivatives, Regulates Inducible Gene Expression in Mammalian Cells

Cited by 235 publications

References 38 publications

Therapeutic immune response induced by intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus and cytokines encoded by adenoviral vectors

Therapeutic immune response induced by intratumoral expression of the fusogenic membrane protein of vesicular stomatitis virus and cytokines encoded by adenoviral vectors

Differential dependence of regulatory volume decrease behavior in rabbit corneal epithelial cells on MAPK superfamily activation

The Dominant-Negative Herpes Simplex Virus Type 1 (HSV-1) Recombinant CJ83193 Can Serve as an Effective Vaccine against Wild-Type HSV-1 Infection in Mice

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