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Biomedical subjects

E Ranieri

Publications and source records attributed to E Ranieri.

At least 19 recordsLinked to original sources
PubMed2006

IL-12p70 and IL-18 gene-modified dendritic cells loaded with tumor antigen-derived peptides or recombinant protein effectively stimulate specific Type-1 CD4+ T-cell responses from normal donors and melanoma patients in vitro.

Although CD4(+) Type-1T helper (Th1) cells secreting interferon-gamma (IFN-gamma) appear to play an essential role in promoting durable antitumor immunity, we have previously shown that patients with cancer exhibit dysfunctional Th1-type responses against epitopes derived from tumor antigens, such as MAGE-A6. Here, we engineered human dendritic cells (DCs) to secrete high levels of the IFN-gamma-inducing cytokines, interleukin (IL)-12p70 and IL-18, via recombinant adenoviral infection to generate an in vitro stimulus capable of promoting previously deficient patient Th1-type responses. Dendritic cells co-infected with Ad.IL-12 and Ad.IL-18 (DC.IL-12/18) were more effective at stimulating MAGE-A6-specific Th1-type CD4(+) T-cell responses than DCs infected with either of the cytokine vectors alone, control Ad.Psi5 virus or uninfected DCs. Furthermore, we show that DC.IL-12/18 loaded with recombinant MAGE-A6 protein (rMAGE) and used as in vitro stimulators promote Th1-type immunity that is frequently directed against multiple MAGE-A6-derived epitopes. The superiority of DC.IL-12/18-based stimulations in melanoma patients was independent of disease stage or current disease status. Based on these results, we believe this modality may prove clinically useful as a vaccine platform to promote the recovery of tumor antigen-specific, Th1-type CD4(+) T-cell responses in patients with cancer.

Adenoviridae↗
PubMed2003

Hydraulics of sub-superficial flow constructed wetlands in semi arid climate conditions.

This paper reports the evaluation of the hydraulics of two constructed wetland (cw(s)) plants located in Apulia (the South Eastern Italy region characterized by semi arid climate conditions). These fields were planted with Phragmites australis hydrophytes and are supplied with local secondary wastewater municipal treatment plant effluent. Each plant--Kickuth Root-Zone method based--covers an area of approx. 2,000 m2. The evapotranspiration phenomenon has been evaluated within perforated tubes fixed to the field bottom and very high values--up to 40 mm/d--were found. Hydraulic conductivity has been evaluated by in situ measurements at different field points. Hydraulic gradients and the piezometric curve within the field are also reported.

Climate↗
PubMed2002

Human herpes virus-like particles in pityriasis rosea lesions: an electron microscopy study.

BACKGROUND: In a previous study we detected virions with electron microscopy features of human herpes viruses in the supernatant of cocultured mononuclear cells from patients with acute pityriasis rosea. Because of their morphology and of polymerase chain reaction studies, we ascribed them to human herpes virus 7. OBJECTIVE: To find such virions in the lesional skin of pityriasis rosea patients. METHODS: Skin specimens from lesions of 21 patients with acute pityriasis rosea were examined by elecron microscopy. RESULTS: In 15 (71%) patients, human herpes virus particles in various stages of morphogenesis were detected. Mature enveloped virions appeared as typical human herpes virus virions, measuring about 160-200 nm in diameter and containing an electrodense cylindrical core, a capsid, an envelope with typical spikes and a very distinct tegument layer between the capsid and the envelope. They were very similar to those we reported in the supernatant of co-cultured circulating mononuclear cells from patients with pityriasis rosea. CONCLUSION: Our results confirm our previous findings and provides further evidence of a viral etiology for pityriasis rosea.

Herpesvirus 7, Human↗
PubMed2001

gp100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+T cells.

CD4+ T cells modulate the magnitude and durability of CTL responses in vivo, and may serve as effector cells in the tumour microenvironment. In order to identify the tumour epitopes recognized by tumour-reactive human CD4+ T cells, we combined the use of an HLA-DR4/peptide binding algorithm with an IFN-gamma ELISPOT assay. Two known and three novel CD4+ T cell epitopes derived from the gp 100/pmel17 and tyrosinase melanocyte-associated antigens were confirmed or identified. Of major interest, we determined that freshly-isolated PBMC frequencies of Th1-type CD4+ T recognizing these peptides are frequently elevated in HLA-DR4+ melanoma patients (but not normal donors) that are currently disease-free as a result of therapeutic intervention. Epitope-specific CD4+ T cells from normal DR4+ donors could be induced, however, after in vitro stimulation with autologous dendritic cell pulsed with antigens (peptides or antigen-positive melanoma lysates) or infected with recombinant vaccinia virus encoding the relevant antigen. Peptide-reactive CD4+ T cells also recognized HLA-DR4+ melanoma cell lines that constitutively express the relevant antigen. Based on these data, these epitopes may serve as potent vaccine components to promote clinically-relevant Th1-type CD4+ T cell effector function in situ.

Adult↗
PubMed2001

Protease-activated receptor 1 and plasminogen activator inhibitor 1 expression in chronic allograft nephropathy: the role of coagulation and fibrinolysis in renal graft fibrosis.

BACKGROUND: Chronic allograft nephropathy (CAN), the major cause of renal graft failure, frequently displays extensive interstitial fibrin deposition. Little is known in regard to the cause of the altered coagulation/fibrinolysis balance and its relevance in the pathogenesis of CAN. Thrombin, present within the fibrin clots, can interact with a specific receptor, protease-activated receptor 1 (PAR-1), and modulate a variety of cell functions. On the other hand, the derangement of the fibrinolytic system may directly affect extracellular matrix (ECM) degradation. METHODS: In the present study, we investigated, by in situ hybridization, PAR-1 gene expression and the mRNA levels for tissue factor and plasminogen activator inhibitor 1 (PAI-1), two key regulatory molecules of coagulation and fibrinolysis, in 16 CAN biopsies and in 10 normal human kidney grafts. The thrombin-induced transforming growth factor beta (TGF-beta) gene and protein expression in proximal tubular cells (PTC) was investigated by Northern blotting and ELISA, respectively. RESULTS: Fibrin deposits, absent in normal grafts, were observed in the interstitial space and arterial wall of CAN. Tissue factor gene expression was not increased either at the vascular or at the interstitial level in CAN. On the contrary, PAI-1 gene expression, barely detectable in control tissue, was strikingly increased in CAN, with a distribution resembling the pattern of fibrin deposition. Note that PAI-1 gene expression was directly correlated with the degree of interstitial fibrosis. In addition, fibrin deposits were strictly associated with a marked increase of PAR-1 gene expression in endothelial cells and PTC. The tubular expression of PAR-1 was significantly higher in Banff grade II-III than in grade I. In vitro, incubation of PTC with thrombin caused a significant up-regulation of TGF-beta gene expression, followed by an increased TGF-beta release into the supernatant. Interestingly, urine from CAN patients contained significantly higher levels of TGF-beta. CONCLUSIONS: Fibrin deposits in CAN may result from the increased expression of PAI-1 and the subsequent inhibition of fibrinolysis. The reduced fibrinolysis may cause, in turn, a decreased ECM turnover. Finally, thrombin, preserved in the active form within the fibrin clots, may interact with PAR-1 highly expressed on PTC and induce an up-regulation of ECM deposition in a TGF-beta-dependent manner.

Chronic Disease↗
PubMed2000

Mature dendritic cells pulsed with freeze-thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4(+) and CD8(+) T lymphocyte responses.

Immunotherapy trials targeting the induction of tumor-reactive T-cell responses in cancer patients appear to hold significant promise. Because nonmutated lineage-specific antigens and mutated idiotypic antigens may be coexpressed by tumor cells, the use of autologous tumor material to promote the broadest range of antitumor T-cell specificities has significant clinical potential in cancer vaccination trials. As a model for vaccination in the cancer setting, we chose to analyze the promotion of T-cell responses against Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line (B-LCL)-derived antigens in vitro. A series of bulk antigenic formats (freeze-thaw lysate, trifluoroacetic acid lysate, extracted membranes, affinity-purified MHC class I- and class II-presented peptides, acid-eluted peptides) prepared from EBV B-LCLs were tested for their ability to stimulate EBV B-LCL-reactive CD4(+) and CD8(+) T lymphocytes in vitro when pulsed onto autologous dendritic cells (DCs). DC presentation of freeze-thaw lysate material derived from (either autologous or allogeneic) EBV B-LCLs with an Mr of 10 kd or larger stimulated optimal anti-EBV B-LCL responsiveness from freshly isolated CD4(+) and CD8(+) peripheral blood T cells. These in vivo "memory" T-cell responses were observed only in EBV-seropositive donors. CD4(+) T-cell responses to lysate-pulsed DCs were Th1 type (ie, strong interferon-gamma and weak interleukin-5 responses). While CD8(+) T-cell responses were also observed in interferon-gamma Elispot assays and in cytotoxicity assays, these responses were of low frequency unless the DC stimulators were induced to "mature" after being fed with tumor lysates. Optimal-length, naturally processed, and MHC class I- or class II-presented tumor peptides were comparatively poorly immunogenic in this model system. (Blood. 2000;96:1857-1864)

Antigens, Neoplasm↗
PubMed2000

Tissue factor, plasminogen activator inhibitor-1, and thrombin receptor expression in human crescentic glomerulonephritis.

Glomerular fibrin deposition is a common histological feature of crescentic glomerulonephritis (CGN). Tissue factor (TF) is the most powerful activator of the coagulation system, whereas plasminogen activator inhibitor (PAI)-1 is a key modulator of the fibrinolytic pathway. Thrombin, released locally as the final step of the coagulation cascade and trapped within the fibrin clots, can induce the activation of glomerular cells, through the interaction with a specific receptor. To investigate the mechanisms underlying coagulation cascade activation and fibrin deposition and the role of this phenomenon in the pathogenesis of human CGN, TF, PAI-1, and thrombin receptor expression were studied in CGN biopsy specimens. Glomerular TF gene and protein expression were strikingly increased in CGN, in particular within the crescents and in the mesangial area, with the same distribution of fibrin deposits. Interestingly, very few infiltrating mononuclear cells were stained in TF immunohistochemistry. To better evaluate the involvement of monocytes in TF expression, TF mRNA and CD68 protein were studied by an in situ hybridization/immunohistochemistry combined technique. Only 16% of the cells expressing TF mRNA were CD68 positive. However, most of the TF signal was localized in the proximity of monocytes, suggesting that soluble mediator(s) released by these cells could induce TF expression. Indeed, interleukin-1 (IL-1), one of the main monocyte-derived cytokines, upregulated TF mRNA levels in cultured human mesangial cells in a time-dependent manner. Moreover, a striking increase in IL-1 expression was present within the cellular crescents in CGN biopsy specimens. Finally, we observed a marked upregulation of both PAI-1 and thrombin receptor mRNA levels in CGN with a pattern resembling TF and fibrin distribution. Surprisingly, thrombin receptor protein expression was strikingly downregulated in CGN, suggesting its continuous activation and degradation. In conclusion, we can hypothesize that TF and PAI-1, mainly expressed by resident cells, may play a pivotal role in the development and preservation of fibrin deposits in CGN. In addition, thrombin, released locally and accumulated within the fibrin clots, may represent a pathogenetic mediator of crescentic lesions.

Adolescent↗
PubMed2000

MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy.

BACKGROUND: Obstructive nephropathy is characterized at the histologic level by tubular atrophy and interstitial monocyte infiltration. The molecular mechanisms underlying these histologic changes are still poorly defined. Epidermal growth factor (EGF) produced by tubular cells seems to play a pivotal role in the modulation of tubular cell growth, while monocyte chemotactic peptide-1 (MCP-1) is a powerful and specific chemotactic and activating factor for monocytes. METHODS: Twenty-four patients with congenital ureteropelvic junction obstruction [UPJO; 10 with recurrent urinary tract infection (UTI) and 10 with no UTI] and 15 healthy children were studied. Diagnosis was made by renal ultrasound, intravenous pielography, and MAG3 scan. Urinary samples were collected before and after surgery. In 10 patients, urine was also collected directly from the affected pelvis at the time of surgery. Urinary EGF and MCP-1 levels were measured by enzyme-linked immunosorbent assay. MCP-1 and EGF gene expression were evaluated by in situ hybridization in 15 biopsies from congenital UPJO and in 10 normal kidneys. RESULTS: In normal kidneys, there was a high expression of EGF mRNA, whereas MCP-1 mRNA was undetectable. MCP-1 gene expression was strikingly increased at the tubulointerstitial level in UPJO biopsies compared with controls and was directly correlated with the extent of monocyte infiltration. In addition, UPJO kidney sections showed a marked reduction in EGF gene expression that was directly correlated with the degree of tubular damage. EGF urine concentration was significantly reduced in UPJO when compared with control and directly correlated with its renal gene expression. On the other hand, the MCP-1 urine concentration was strikingly increased in UPJO patients. It is noteworthy that a significant and inverse correlation was observed between the MCP-1 concentration in the urine collected from the obstructed pelvis and the MAG3 clearance of the obstructed kidney (r = -0.76). The presence of recurrent UTI was associated with a significantly higher MCP-1 excretion and a slight reduction in EGF urine concentration. The surgical correction of UPJO was followed by an improvement of renal function together with a significant reduction in MCP-1 excretion and a marked increase in EGF urine concentrations. Interestingly, EGF urine concentration measured before surgery was significantly correlated with the difference between the MAG3 clearance of the obstructed kidney before and after surgery. CONCLUSIONS: MCP-1 and EGF seem to be involved in the pathogenesis of tubulointerstitial damage in congenital obstructive nephropathy, and their urine excretion may represent a powerful prognostic marker in this form of renal disease.

Adolescent↗
PubMed2000

The impact of maternal serum screening on the birth prevalence of Down's syndrome and the use of amniocentesis and chorionic villus sampling in South Australia.

OBJECTIVES: To describe the impact of maternal serum screening on the birth prevalence of Down's syndrome and on the use of amniocentesis and chorionic villus sampling in South Australia. DESIGN: A descriptive population-based study. SETTING: South Australia (population 1.48 million persons; approximately 20,000 births per year). PARTICIPANTS: Women who had births or terminations of pregnancy with Down's syndrome in 1982-1996, women who had maternal serum screening in 1991-1996, amniocentesis or chorionic villus sampling in 1986-1996. METHODS: Analysis of data from multiple sources on maternal serum screening, amniocentesis and chorionic villus sampling, births and terminations of pregnancy. MAIN OUTCOME MEASURES: Total prevalence and birth prevalence of Down's syndrome each year in 1982-1996; proportion of pregnant women using maternal serum screening in 1991-1996, and proportion using amniocentesis and chorionic villus sampling by indication in 1986-1996, by age group. RESULTS: Use of maternal serum screening for Down's syndrome increased from 17% when introduced in 1991 to 76% of women who gave birth in 1996. Between 1982 and 1986 and 1996, terminations of pregnancy for fetal Down's syndrome increased from 7.1 % to 75% and the birth prevalence of Down's syndrome fell by 60% from 1.05 to 0.42 per 1,000 births, against the background of an increase in total prevalence due to increasing maternal age. The use of amniocentesis increased from 5.8% in 1991 to 10.1% in 1996 mainly due to the increase among women younger than 35 years with maternal serum screening as the main reason. The increasing chorionic villus sampling rate among younger women stabilised at 0.4%, while the rate among older women decreased from 11.0% to 7.4%. CONCLUSIONS: The introduction of maternal serum screening in South Australia has resulted in increased use of any prenatal testing for Down's syndrome from about 7% (mainly older women having amniocentesis or chorionic villus sampling) to 84% of women (about 8% having direct amniocentesis or chorionic villus sampling and 76% having maternal serum screening first). This has resulted in a significant fall in the birth prevalence of Down's syndrome. maternal serum screening was the first indication of Down's syndrome for about half the terminations of pregnancy for Down's syndrome in 1993-1996, including three quarters of those in younger women.

Adult↗
PubMed2000

Determination of acid alpha-glucosidase protein: evaluation as a screening marker for Pompe disease and other lysosomal storage disorders.

BACKGROUND: In recent years, there have been significant advances in the development of enzyme replacement and other therapies for lysosomal storage disorders (LSDs). Early diagnosis, before the onset of irreversible pathology, has been demonstrated to be critical for maximum efficacy of current and proposed therapies. In the absence of a family history, the presymptomatic detection of these disorders ideally can be achieved through a newborn screening program. One approach to the development of such a program is the identification of suitable screening markers. In this study, the acid alpha-glucosidase protein was evaluated as a marker protein for Pompe disease and potentially for other LSDs. METHODS: Two sensitive immunoquantification assays for the measurement of total (precursor and mature) and mature forms of acid alpha-glucosidase protein were used to determine the concentrations in plasma and dried blood spots from control and LSD-affected individuals. RESULTS: In the majority of LSDs, no significant increases above control values were observed. However, individuals with Pompe disease showed a marked decrease in acid alpha-glucosidase protein in both plasma and whole blood compared with unaffected controls. For plasma samples, this assay gave a sensitivity of 95% with a specificity of 100%. For blood spot samples, the sensitivity was 82% with a specificity of 100%. CONCLUSIONS: This study demonstrates that it is possible to screen for Pompe disease by screening the concentration of total acid alpha-glucosidase in plasma or dried blood spots.

Biomarkers↗
PubMed1999

Identification of naturally processed and HLA-presented Epstein-Barr virus peptides recognized by CD4(+) or CD8(+) T lymphocytes from human blood.

The broad clinical implementation of cancer vaccines targeting the induction of specific T cell-mediated immunity is hampered because T cell defined tumor-associated peptides are currently available for only a restricted range of tumor types. Current epitope identification strategies require a priori the generation of T "indicator" cell lines that specifically recognize the tumor antigenic epitope in in vitro assay systems. An alternative to this strategy is the use of "memory" T cells freshly isolated from the peripheral blood of patients with cancer in concert with sensitive effector cell readout assays (such as the cytokine enzyme-linked immunospot assay) and MS to identify relevant peptide epitopes. In a model system, we have evaluated the capacity of natural Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line-extracted peptides to activate "memory" viral-specific CD4(+) or CD8(+) T cells freshly isolated from the blood of an EBV-seropositive individual using the IFN-gamma enzyme-linked immunospot assay. After HPLC fractionation and loading onto autologous dendritic cells, multiple naturally processed HLA class I and II-associated lymphoblastoid cell line-derived peptides were isolated that were capable of inducing IFN-gamma spot production by "memory" T lymphocytes. Using MS analysis on a HPLC fraction recognized by CD8(+) T cells, we were able to sequence natural 9-, 10-, and 11-mer peptides naturally processed from the latent EBV antigen LMP-2 (latent membrane protein-2) and presented in the context of HLA-A2. This approach provides a useful methodology for the future identification of MHC-presented viral and tumor epitopes using freshly isolated patient materials.

CD4-Positive T-Lymphocytes↗
PubMed1999

Low-density lipoproteins enhance transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemotactic protein-1 (MCP-1) expression induced by cyclosporin in human mesangial cells.

Cyclosporin (CsA) is widely used in the treatment of renal disease and transplantation, which are often complicated by alterations of lipid metabolism. Both chronic administration of CsA and hyperlipidaemia have been shown to evoke an early macrophage influx and have progressively led to glomerular and interstitial sclerosis. MCP-1 is the major monocyte chemoattractant secreted by stimulated mesangial cells and TGF-beta 1 is a key mediator of fibrogenesis in chronic progressive renal fibrosis. Thus, the combined effect of CsA and low-density lipoprotein (LDL) on the gene and protein expression of MCP-1 and TGF-beta 1 in cultured human mesangial cells (HMC) was explored. Both agents induced an early and persistent increase of MCP-1 and TGF-beta 1 mRNA levels and protein release. The simultaneous addition of CsA and LDL did not display any additive effect on target gene expression, but it caused a synergistic effect on MCP-1 and TGF-beta 1 protein secretion into culture medium. On the other hand, CsA and LDL had different effects on cell proliferation: the latter increased DNA synthesis, whereas CsA inhibited both spontaneous and mitogen-stimulated mesangial cell growth. The study concludes that CsA and LDL display an additive effect on TGF-beta 1 and MCP-1 synthesis and release by HMC, thus possibly co-operating to induce an early macrophage influx and the subsequent mesangial expansion and increased extracellular matrix deposition. However, in contrast they seem to modulate HMC proliferation differently, which is a further critical event intimately involved in the development of glomerulosclerosis.

Cell Division↗
PubMed1999

Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells.

BACKGROUND: Angiotensin II (Ang II) has been shown to be implicated in the development of renal fibrosis in several forms of chronic glomerulonephritides, but the precise mechanisms of its effects remain unclear. It has recently been reported that Ang II stimulates the expression of plasminogen activator inhibitor-1 (PAI-1) in several cell lines. PAI-1 is a major physiological inhibitor of the plasminogen activator/plasmin system, a key regulator of fibrinolysis and extracellular matrix (ECM) turnover. PAI-1 induction by Ang II in endothelial cells seems to be mediated by Ang IV via a receptor that is different from Ang II type 1 and 2 receptors (AT1 and AT2). METHODS: In this study, we sought to evaluate the effects of Ang IV on PAI-1 gene and protein expression in a well-characterized and immortalized human proximal tubular cell line (HK2) by Northern blot and enzyme-linked immunosorbent assay. RESULTS: Ang IV stimulated PAI-1 mRNA expression, whereas it did not induce a significant increase in tritiated thymidine uptake after 24 hours of incubation. This effect was dose and time dependent. Ang IV (10 nM) induced a 7.8 +/- 3.3-fold increase in PAI-1 mRNA expression. The PAI-1 antigen level was significantly higher in conditioned media and the ECM of cells treated with Ang II and Ang IV than in control cells (both P < 0.02). Although Ang II induced a 4.2 +/- 2. 1-fold increase in PAI-1 mRNA expression, its effect underwent a dose-dependent reduction when amastatin, a potent inhibitor of the endopeptidases that catalyzes the conversion of Ang II to Ang IV, was added. In contrast, amastatin was not able to prevent the expression of PAI-1 mRNA induced by Ang IV. Finally, pretreatment of HK2 cells with losartan and N-Nicotinoyl-Tyr-N3-(Nalpha-CBZ-Arg)-Lys-His-Pro-Ile, the specific antagonists of AT1 and AT2 receptors, failed to modify PAI-1 mRNA expression as induced by Ang II. CONCLUSIONS: Our results demonstrate that Ang II stimulates PAI-1 mRNA expression and the production of its protein in human proximal tubular cells. This is mainly-if not exclusively-due to Ang IV, which acts on a receptor that is different than AT1 or AT2. Therefore, it can be hypothesized that the induction of PAI-1 by Ang IV may be implicated in the pathogenesis of renal interstitial fibrosis in several forms of chronic glomerulonephritides.

Angiotensin II↗
PubMed1999

Dendritic cells transduced with an adenovirus vector encoding Epstein-Barr virus latent membrane protein 2B: a new modality for vaccination.

Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignancies, particularly in immunocompromised hosts. As a strategy for stimulating immunity against EBV for the treatment of EBV-associated tumors, we have genetically engineered dendritic cells (DC) to express EBV antigens, such as latent membrane protein 2B (LMP2B), using recombinant adenovirus vectors. CD8(+) T lymphocytes from HLA-A2.1(+), EBV-seropositive healthy donors were cultured with autologous DC infected with recombinant adenovirus vector AdEGFP, encoding an enhanced green fluorescent protein (EGFP), or AdLMP2B at a multiplicity of infection of 250. After 48 h, >95% of the DC were positive for EGFP expression as assessed by fluorescence-activated cell sorting analysis, indicating efficient gene transfer. AdLMP2-transduced DC were used to stimulate CD8(+) T cells. Responder CD8(+) T cells were tested for gamma interferon (IFN-gamma) release by enzyme-linked spot (ELISPOT) assay and cytotoxic activity. Prior to in vitro stimulation, the frequencies of T-cells directed against two HLA-A2-presented LMP2 peptides (LMP2 329-337 and LMP2 426-434) were very low as assessed by IFN-gamma spot formation (T-cell frequency, <0.003%). IFN-gamma ELISPOT assays performed at day 14 showed a significant (2-log) increase of the day 0 frequency of T cells reactive against the LMP2 329-337 peptide, from 0.003 to 0.3 (P < 0.001). Moreover, specific cytolytic activity was observed against the autologous EBV B-lymphoblastoid cell lines after 21 days of stimulation of T-cell responders with AdLMP2-transduced DC (P < 0.01). In summary, autologous mature DC genetically modified with an adenovirus encoding EBV antigens stimulate the generation of EBV-specific CD8(+) effector T cells in vitro, supporting the potential application of EBV-based adenovirus vector vaccination for the immunotherapy of the EBV-associated malignancies.

Adenoviruses, Human↗