Chemistry: molecular biology and microbiology – Vector – per se
Patent
1993-11-08
1998-02-17
Guzo, David
Chemistry: molecular biology and microbiology
Vector, per se
536 2372, C12N 1586, C07H 2104
Patent
active
057190542
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to recombinant virus vectors. In particular, it relates to recombinant virus vectors designed to overcome the problem of recombination between homologous nucleotide sequences. It also relates to recombinant virus vectors encoding human papillomavirus proteins; to immunotherapeutics and vaccines for conditions associated with HPV infection; to the production of a virus (e.g. vaccinia virus) engineered to express antigens encoded by human papillomavirus types 16 and 18 and to immunotherapeutics and vaccines for cervical cancer.
BACKGROUND OF THE INVENTION
In recent years, strong evidence has been adduced for a link between cervical carcinoma and infection with certain types of human papillomavirus (HPV), particularly with types 16, 18, 31, 33 and 35 (Gissman et al., Cancer Cells 5,275, 1987). This is based on hybridisation studies which have indicated that more than 85-90% of biopsies from cervical tumours can be shown to contain papillomavirus DNA. HPV16 DNA is most commonly found (in about 60% of tumours) with HPV18 the next most frequent (about 20%) and the other types accounting for a further 5-10%. In many instances, tumour cells from the biopsies do not however, contain the complete genome, but rather a deleted form. The extent and location of the deleted information within the virus genome is variable, but a general feature is the retention of the part of the genome encoding the E7 protein (Schwarz et al., Nature 314, 111, 1985). In addition, the adjacent E6-encoding region is usually present. The ubiquitous presence of the E7-encoding region in tumour cells suggests that the protein product of this gene might play a role in the induction or maintenance of the transformed phenotype. Indeed in most cell lines established from tumour biopsies, expression of the E7 gene can be detected (Smotkin & Wettstein, PNAS, 83, 4680, 1986). Furthermore, it has been shown that the E7 gene product can bind to the retinoblastoma (Rb) gene product, a recognised "anti-oncogene" in normal human cells (Munger et al., EMBO J. 8,4099, 1989). This strengthens the belief that E7 is directly involved in cell transformation.
The presence and expression of the E7 and E6 genes in tumour cells derived from cervical carcinoma biopsies, suggests the possibility that these proteins could be potential targets for the immunological recognition of the tumour cells. It is well known that viral proteins produced inside mammalian cells can be processed through a host cell pathway to short peptides, which then form a complex with host Major Histocompatibility Complex (MHC) Class 1 molecules and are transported to the cell surface. These complexes may then present a target for recognition by the host immune system. Interaction of the complex with the receptor molecule on the surface of cytotoxic T cells (the T cell receptor) can then lead to activation of the T cells to proliferate or to destroy the recognised cell. It is possible, therefore, that the presence in the body of a population of cytotoxic T lymphocytes (CTLs) which are capable of recognising cells expressing the HPV E6 and/or E7 proteins could afford protection against the development and proliferation of cervical tumours. Indeed it has been reported that normally oncogenic mouse cells engineered to express the HPV E7 protein are unable to form tumours in mice which have been previously immunised with non-tumorigenic E7-expressing cells, and that this rejection is mediated by CD8+lymphocytes (CTLs) (Chen et al., PNAS 88, 110, 1991). Further, the generation of an active population of such cells subsequent to tumour initiation could result in regression of the tumour.
There are numerous reports on the construction of recombinant viruses e.g. vaccinia viruses containing, and expressing foreign genes (Mackett & Smith, J. gen. Virol. 67,2067, 1986), and several reports of the use of these recombinant viruses to generate effective immune responses against the expressed foreign antigens. A particular advantage of this route for delivery
REFERENCES:
Meneguzzi et al. "Vaccinia Recombinants Expressing Early Bovine Papilloma Virus (BPVI) Proteins: Retardation of BPVI Tumour Development", Vaccine, vol. 8, Jun. 1990, pp. 199-204.
Meneguzzi et al. "Immunization Against Human Papillomovirus Type 16 Tumor Cells with Recombinant Vaccinia Viruses Expressing E6 and E7", Virology, vol. 181, Mar. 1991, pp. 62-69.
Chen et al., Proc. Natl. Acad. Sci. USA, 88 110-114 (1991) "Human papillomavirus type 16 nucleoprotein E7 is a tumor".
Lathe et al., Nature, 326 878-880 (1987) "Tumour prevention and rejection with recombinant vaccinia".
Mackett et al., Journal of Virology, 49(3) 857-864 (1984) "General method for production and selection of infectious vaccinia virus recombinants expression foreign genes".
Rixon, et al., Journal of General Virology, 71 2931-2939 (1990) "Insertion of DNA sequences at a unique restriction enzyme site engineered for vector purposes into the genome of herpex simplex virus type 1".
Sadovnikova et al., International Immunology, 6(2) 289-296 (1994) "Limitations of predictive motifs revealed by cytotoxic T lymphocyte epitope mapping of the human papilloma virus E7 protein".
Eloit et al., Journal of General Virology, 71 2425-2431 (1990) "Construction of a defective adenovirus vector expressing the pseudorables virus glycoprotein gp50 and its use as a live vaccine".
Ballay et al., The EMBO Journal, 4 (13B) 3861-3865 (1985) "In vitro and in vivo synthesis of the hepatitis B virus surface antigen and of the receptor for polymerized human serum albumin from recombinant human adenoviruses".
Chesters et al., Abstract--J. Gen. Virol., 71(2) 449-453 (1990) "Analysis of human papillomvirus type 16 open reading frame E7 immortalizing function in rat embryo fibroblast cells".
Naito et al. Biochem. and Biophys. Res. Comm. 174, 1 pp. 305-312 (1991) "Homologous recombination in bovine papillomavirus shuttlevector: Effect of relative orientation of substrate sequences".
Kitamura, et al. Mol. Gen. Genet 222 pp. 185-191 (1990) "Homologous recombination in a mammalian plasmid".
Storey, et al. The EMBO Journal 7, 6 pp. 1815-1820 (1988) "Comparison of the in vitro transforming activities of human papillomavirus types".
Jones, et al. Jour. Bio. Chem. 265, 22 pp. 12782-12785 (1990) "Identification of HPV-16 E7 peptides that are potent antagonists of E7 binding to the retinoblastoma suppressor protein".
Boursnell Michael E.
Inglis Stephen C.
Munro Alan J.
Brunelle Jan P.
Cantab Pharmaceuticals Research Limited
Dreger Walter H.
Guzo David
LandOfFree
Recombinant virus vectors encoding human papillomavirus proteins does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Recombinant virus vectors encoding human papillomavirus proteins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Recombinant virus vectors encoding human papillomavirus proteins will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1783440