Mice which coexpress human papillomavirus type 16 E7 and HLA A2.1 in peripheral squamous epithelium and thymic cortical epithelium are tolerant at the cytotoxic T-lymphocyte (CTL) level to E7 epitopes restricted through HLA A*0201 and H-2(b) (T. Doan, M. Chambers, M. Street, G. J. Fernando, K. Herd, P. Lambert, and R. Tindle, Virology 244:352-364, 1998). Here we used bone marrow-reconstituted r...

OBJECTIVE In most cervical cancers, human papillomaviruses (HPVs) are identified. The E6 and E7 genes of HPVs encode proteins, that interfere with the function of the tumor suppressor proteins p53 and Rb. We are exploring the potential use of antisense HPV RNA transcripts for gene therapy for HPV-positive cervical cancers. METHODS Via a recombinant adenoviral vector, Ad5CMV-HPV 16 AS, we intr...

High-risk human papillomaviruses (HPVs) cause cervical cancer, and while there are good prophylactic vaccines on the market, these are ineffective against established infections, creating a clear need for therapeutic vaccines. The HPV E7 protein is one of the essential oncoproteins for the onset and maintenance of malignancy and is therefore an ideal therapeutic vaccine target. We fused the HPV...

There is strong evidence implicating human papillomavirus type 16 (HPV16) in the genesis of human genital cancer. Viral DNA has been identified in invasive carcinoma of the uterine cervix and in cell lines derived from cervical carcinomas. These sequences are actively transcribed, and translation products corresponding to the early (E)-region genes have been identified. The most abundant viral ...

High-risk human papillomaviruses (hr-HPVs) cause cervical cancer, the fourth most common cancer in women worldwide. A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection and regression in pre-clinical immunization studies. In the current study, we investigated the p...

Disruption of the retinoblastoma (RB) tumor suppressor pathway is a common and important event in breast carcinogenesis. To examine the role of the retinoblastoma protein (pRB) in this process, we created human mammary epithelial cells (HMEC) deficient for pRB by infecting primary outgrowth from breast organoids with the human papillomavirus type 16 (HPV16) E7 gene. HPV16 E7 binds to and inacti...

The human papillomavirus (HPV) E2 protein is an important regulator of viral E6 and E7 gene expression. E2 can repress the viral promoter for E6 and E7 expression as well as block progression of the cell cycle in cancer cells harboring the DNA of "high-risk" HPV types. Although the phenomenon of E2-mediated growth arrest of HeLa cells and other HPV-positive cancer cells has been well documented...

RNA interference using small interfering RNA (siRNA) is an effective means of silencing gene expression in cells. Intradermal administration of nucleic acids via gene gun represents an efficient method for delivering nucleic acids to professional antigen-presenting cells in vivo. In this study, we show that the coadministration of DNA vaccines encoding human papillomavirus type 16 E7 with siRNA...

objective: for immunotherapy of human papillomavirus (hpv) -16-associated cervical cancers the e7 protein is considered a prime candidate. however it is a poor inducer of cytotoxic t-cell response, when being used as a singular antigen in protein vaccination. hence, in this study we focused on the utilization of a vaccine delivery system for prevention or treatment of cervical cancer. materials...

The expression of the high risk HPV18 E6 and E7 oncogenic proteins induces the transformation of epithelial cells, through the disruption of p53 and Rb function. The binding of cellular transcription factors to cis-regulatory elements in the viral Upstream Regulatory Region (URR) stimulates E6/E7 transcription. Here, we demonstrate that the CCAAT-transcription factor NF-Y binds to a non-canonic...