scholarly journals Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation

2017 ◽  
Vol Volume 12 ◽  
pp. 4579-4591 ◽  
Author(s):  
Paola Di Bonito ◽  
Chiara Chiozzini ◽  
Claudia Arenaccio ◽  
Simona Anticoli ◽  
Francesco Manfredi ◽  
...  
Keyword(s):  
Hpv E7 ◽  
Ctl Activity ◽  
Dna Inoculation

Abrogation of IRF-1 response by high-risk HPV E7 protein in vivo

2002 ◽  
Vol 179 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Soo-Jong Um ◽  
Jae-Woong Rhyu ◽  
Eun-Joo Kim ◽  
Kook-Che Jeon ◽  
Eun-Seoung Hwang ◽  
...  
Keyword(s):  
High Risk ◽  
Hpv E7 ◽  
High Risk Hpv

GENERATION OF AN EFFECTIVE IN VIVO CTL RESPONSE USINGVACCINE APPROACHES IN A MODEL OF AUTOIMMUNITY

2008 ◽  
Vol 31 (4) ◽  
pp. 8
Author(s):  
D T Dissanayake ◽  
P S Ohashi
Keyword(s):  
Intracellular Cytokine Staining ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
Single Class ◽  
Ctl Response ◽  
Glucose Levels ◽  
Tissue Antigens ◽  
Ctl Activity

Background: Various interactions between tumours and their environment make it difficult to determine the factors that are essential to the induction of a robust CTL response by immunotherapeutic strategies against tissue antigens. We therefore sought to develop a model of autoimmunity, in which vaccine strategies could be evaluated for their ability to elicit CTL activity towards a model antigen. Methods: Transgenic mice expressing lymphocytic choriomeningitis virus glycoprotein (LCMV-gp) specifically in the insulin-producing beta-islets of the pancreas allowed anti-beta islet CTL responses to be measured by blood glucose levels, tetramer and intracellular cytokine staining. Peptide vaccines consisted of i.v. administration of the known immunodominant epitopesof LCMV-gp alongside dendritic cell (DC) maturation stimuli. DC vaccines consisted of i.v.administration of 2x10^6 mature LCMV-gp peptide-pulsed bone-marrow-derived DC. Results: While administration of antigenic peptides with adjuvants and/or costimulatory molecules were ineffective, DC vaccination induced hyperglycemia in approximately 70% of mice. Interestingly, while a class II epitope was not required for induction of autoimmunity, pulsing with a single class I epitope was insufficient. Furthermore, while tetramer-positive populations could be seen in the blood of peptide-vaccinated mice, no such population is seen in DC-treated mice. Conclusions: The lack of correlation between presence of tetramer-positive populations in the blood and effective beta-islet cell cytolysis underlines the requirement for better markers of CTL activity inclinical trials. These results demonstrate the effectiveness of DC vaccination in this model and allow for further investigation of the factors that direct a strong CD8+ T-cell response towards tissue antigens.

Facilitated DNA inoculation induces anti-HIV-1 immunity in vivo

Vaccine ◽  
1994 ◽  
Vol 12 (16) ◽  
pp. 1545-1550 ◽  
Author(s):  
Leslie Coney ◽  
Bin Wang ◽  
Kenneth E. Ugen ◽  
Jean Boyer ◽  
Daniel McCallus ◽  
...  
Keyword(s):  
Anti Hiv ◽  
Hiv 1 ◽  
Dna Inoculation

scholarly journals HPV E7-mediated NCAPH ectopic expression regulates the carcinogenesis of cervical carcinoma via PI3K/AKT/SGK pathway

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Meng Wang ◽  
Xiaowen Qiao ◽  
Tamara Cooper ◽  
Wei Pan ◽  
Liang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Depth Of Invasion ◽  
Mesenchymal Transition ◽  
Hpv E7

AbstractCervical cancer is one of the most common gynecological tumors in the world, and human papillomavirus (HPV) infection is its causative agent. However, the molecular mechanisms involved in the carcinogenesis of cervical cancer still require clarification. Here we found that knockdown of Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) gene expression significantly inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of cervical cancer cells in vitro, and restrained xenograft tumor formation in vivo. Intriguingly, HPV E7 could form a positive feedback loop with NCAPH. E7 upregulated NCAPH gene expression via E2F1 which initiated NCAPH transcription by binding to its promoter directly. Silencing of NCAPH reduced E7 transcription via promoting the transition of AP-1 heterodimer from c-Fos/c-Jun to Fra-1/c-Jun. Moreover, the E7-mediated NCAPH overexpression was involved in the activation of the PI3K/AKT/SGK signaling pathway. In vivo, NCAPH expression in cervical cancer tissues was significantly higher than which in normal cervix and high-grade squamous intraepithelial lesion (HSIL) tissues, and its expression was significantly correlated with tumor size, depth of invasion and lymph node metastasis. Patients with high NCAPH expression had a significantly better survival outcomes than those with low-expression, suggesting that NCAPH-induced cell proliferation might sensitize cancer cells to adjuvant therapy. In conclusion, our results revealed the role of NCAPH in the carcinogenesis of cervical cancer in vitro and in vivo. The interaction between E7 and NCAPH expands the mechanism of HPV induced tumorigenesis and that of host genes regulating HPV E7.

scholarly journals Recapitulation of the Effects of the Human Papillomavirus Type 16 E7 Oncogene on Mouse Epithelium by Somatic Rb Deletion and Detection of pRb-Independent Effects of E7 In Vivo

2003 ◽  
Vol 23 (24) ◽  
pp. 9094-9103 ◽  
Author(s):  
Scott J. Balsitis ◽  
Julien Sage ◽  
Stefan Duensing ◽  
Karl Münger ◽  
Tyler Jacks ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Transgenic Mice ◽  
Biological Activities ◽  
Human Papillomavirus Type 16 ◽  
Retinoblastoma Tumor Suppressor ◽  
Hpv E7 ◽  
Independent Effects ◽  
Retinoblastoma Tumor ◽  
E7 Oncogene

ABSTRACT Although the human papillomavirus (HPV) E7 oncogene is known to contribute to the development of human cervical cancer, the mechanisms of its carcinogenesis are poorly understood. The first identified and most recognized function of E7 is its binding to and inactivation of the retinoblastoma tumor suppressor (pRb), but at least 18 other biological activities have also been reported for E7. Thus, it remains unclear which of these many activities contribute to the oncogenic potential of E7. We used a Cre-lox system to abolish pRb expression in the epidermis of transgenic mice and compared the outcome with the effects of E7 expression in the same tissue at early ages. Mice lacking pRb in epidermis showed epithelial hyperplasia, aberrant DNA synthesis, and improper differentiation. In addition, Rb-deleted epidermis (i.e., epidermis composed of cells with Rb deleted) exhibited centrosomal abnormalities and failed to arrest the cell cycle in response to ionizing radiation. Transgenic mice expressing E7 in skin display the same range of phenotypes. In sum, few differences were detected between Rb-deleted epidermis and E7-expressing epidermis in young mice. However, when both E7 was expressed and Rb was deleted in the same tissue, increased hyperplasia and dysplasia were observed. These findings indicate that inactivation of the Rb pathway can largely account for E7's phenotypes at an early age, but that pRb-independent activities of E7 are detectable in vivo.

scholarly journals Induction of Humoral and Cellular Immune Responses to the Human Immunodeficiency Type 1 Virus in Nonhuman Primates by in Vivo DNA Inoculation

Virology ◽  
1995 ◽  
Vol 211 (1) ◽  
pp. 102-112 ◽  
Author(s):  
Bin Wang ◽  
Jean Boyer ◽  
Vasantha Srikantan ◽  
Kenneth Ugen ◽  
Lori Gilbert ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nonhuman Primates ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Dna Inoculation

scholarly journals Cutting Edge: Rapid In Vivo CTL Activity by Polyoma Virus-Specific Effector and Memory CD8+ T Cells

2003 ◽  
Vol 171 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Anthony M. Byers ◽  
Christopher C. Kemball ◽  
Janice M. Moser ◽  
Aron E. Lukacher
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Polyoma Virus ◽  
Cutting Edge ◽  
Memory Cd8 T Cells ◽  
Specific Effector ◽  
Ctl Activity

Targeting STAT1 Separates Graft-Versus-Host Disease (GVHD) and Graft-Versus-Leukemia (GVL) Effects in Mice

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2973-2973
Author(s):  
Caisheng Lu ◽  
Huihui Ma ◽  
MeiHua Jin ◽  
Ailing Liu ◽  
Shirong Li ◽  
...  
Keyword(s):  
T Cells ◽  
Target Cells ◽  
Spleen Cells ◽  
Cd8 Cells ◽  
Host Type ◽  
Donor T Cells ◽  
Ifn Γ ◽  
Ctl Activity

Abstract Abstract 2973 We have recently shown that loss of STAT1 signaling in donor T cells significantly reduces acute GVHD in both MHC-mismatched and mHA-mismatched BMT and is associated with increased expansion of Treg cells. In this study we further addressed the role of STAT1 in GVL reactions and the underlying mechanisms. We first sought to delineate the role of STAT1 in the generation of CD8+ CTL against host-type spleen cells and A20 lymphoma targets using standard CML assays. Whole spleen cells (SPCs) or CD8+ selected STAT1+/+ or STAT1−/− cells from 129Sv mice (H2b) were stimulated for 5 days with irradiated BALB/c (H2d) spleen cells or A20 cells and then assessed for CTL activity against 51Cr-labelled target cells. STAT1-deficient SPCs appeared to have reduced CTL activity against host SPCs and host type A20 lymphoma cells compared to STAT1+/+ splenocytes. In contrast, isolated STAT1-deficient CD8+ cells had significantly increased CTL activity against both host-type targets and A20 cells. We then assessed the role of STAT1 in mediating GVL effects in vivo using a fully MHC-mismatched (129 [H2b]→BALB/c [H2d]) strain combination and the A20 lymphoma model. Lethally irradiated (800rad) BALB/c mice received T cell-depleted (TCD) wildtype 129 bone marrow cells (BMCs, 5×10E6) plus pan-T cells (5×10E5) from either 129.STAT1−/− or 129.STAT1+/+ donors. In addition, recipients were injected with 5×10E5 luciferase-expressing A20 lymphoma cells (A20-luc) on day 0. As expected animals receiving STAT1-deficient T cells showed significantly reduced GVHD-induced mortality (mean survival time [MST] not reached versus 11 days, p<0.001). Mice receiving TCD BMCs alone plus A20-luc had a MST of 25 days after BMT with all animals succumbing to death by tumor. Mice receiving TCD BMCs plus wild type pan-T cells and challenged with A20-luc died before day 20 due to severe GVHD (MST 10 days post-BMT). In contrast, mice receiving STAT1−/− pan-T and A20-luc cells showed significantly prolonged survival (MST 43 days post-BMT, p=0.0027, Log-rank test). Sustained GVL effects of STAT1-deficient splenocytes against A20-luc cells were further confirmed by bioluminescence imaging on days +10 and days +20 post-BMT. As we recently reported that absence of STAT1 in donor lymphocytes impairs Th1 differentiation and enhances Treg generation in CD4+ lymphocytes, we further investigated wether absence of STAT1 would influence differentiation of CD8+ cells. Our data revealed that CD8+ cells lacking STAT1 failed to be activated into IFN- γ-producing cells upon anti-CD3/CD28 stimulation. However, when cultured under Th1 conditions (i.e. in the presence of IL-12 and neutralizing anti-IL4 antibodies), IFN- γ secretion could be restored. This intact CD8+ cell differentiation was also observed in vivo on day +6 post-BMT in recipients of STAT1−/− BMCs plus splenocytes where we were able to detect comparable levels of IFN- γ-expressing CD8+ cells compared to recipients of STAT1+/+ donor grafts in both MHC- and mHA-mismatched BMT settings. Furthermore, we could demonstrate preserved CTL function of STAT1-deficient CD8+ in vivo. For that purpose BALB/c mice were reconstituted with 129 wildtype BMC together with either STAT1+/+ or STAT1−/− CD8 T cells. On day+37 post-BMT mice were infused with CFSE-labelled host splenocytes as targets cells. Similar clearance of CFSE-labelled target cells was observed between STAT1-deficient and STAT1 wildtype cells. These results suggest that STAT1 in donor T cells may serve as a potential target to separate GVHD and GVL through promoting Treg generation from CD4+ cells while conserving or even promoting Tc1 differentiation of CD8+ cells. Disclosures: Lentzsch: Celgene: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; Centocor Ortho Biotech: Research Funding.

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