Genetic immunization against cervical carcinoma: induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7
T. Daemen et al., Genetic immunization against cervical carcinoma: induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7, GENE THER, 7(21), 2000, pp. 1859-1866
infection of genital epithelial cells with human papillomavirus (HPV) types
16 and 18 is closely associated with the development of cervical carcinoma
. The transforming potential of these high-risk HPVs depends on the express
ion of the E6 and E7 early viral gene products. Since the expression of E6
and E7 is selectively maintained in premalignant and malignant cervical les
ions these proteins are attractive candidates for immunotherapeutic and pro
phylactic strategies. This report describes the construction, characterizat
ion and the in vive immunotherapeutic potential of recombinant Semliki Fore
st virus (SFV) expressing the HPV16 E6 and E7 proteins (SFV-EGE7). Western
blot analysis and immunofluorescence staining demonstrated expression of E6
and E7 in BHK cells infected with SFV-EGE7. Immunization of mice with SFV-
EGE7 resulted in an efficient in vive priming of HPV-specific CTL activity.
The induced CTL lysed murine tumor cells transformed with the HPV16 genome
and EL4 cells loaded with an immunodominant class I-binding HPV E7 peptide
. CTLs could reproducably be induced by immunization with three injections
of as few as 10(5) infectious units of SFV-EGE7. Protection from tumor chal
lenge was studied using the tumor cell line TC-1. immunization with 5 x 10(
6) SFV-EGE7 particles protected 40% of the mice from tumor challenge. These
results indicate that E6E7 expression by the efficient and safe recombinan
t SFV system represents a promising strategy for immunotherapy or immunopro
phylaxis of cervical carcinoma.