Construction and characterisation of a recombinant vaccinia virus expressing human papillomavirus proteins for immunotherapy of cervical cancer.
The presence and consistent expression of the genes encoding the human papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours presents the opportunity for an immunotherapeutic approach for control of the disease. This report describes the construction and characterisation of a recombinant vaccinia virus designed to express modified forms of the E6 and E7 proteins from HPV16 and HPV18, the viruses most commonly associated with cervical cancer. The recombinant virus (designated TA-HPV) was based on the Wyeth vaccine strain of vaccinia, and was shown to express the desired gene products. Studies in mice indicated that the recombinant virus was less neurovirulent than the parental virus and was capable of inducing an HPV-specific CTL response. This pre-clinical evaluation has provided a basis for the initiation of human trials in cervical cancer patients.
Boursnell
M E
ME
Cantab Pharmaceuticals Research Ltd., Cambridge, UK.
Rutherford
E
E
Hickling
J K
JK
Rollinson
E A
EA
Munro
A J
AJ
Rolley
N
N
McLean
C S
CS
Borysiewicz
L K
LK
Vousden
K
K
Inglis
S C
SC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019496:Cancer Vaccines / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology / Q000517:prevention & control*; D004268:DNA-Binding Proteins; D005260:Female; D005814:Genes, Viral; D005822:Genetic Vectors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000628:therapy; D014614:Vaccines, Synthetic / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics; D014774:Virulence
D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins