Biolistic DNA Vaccination Against Cervical Cancer
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The development of cervical cancer is associated with infection by oncogenic human papillomaviruses (HPVs), of which type 16 (HPV16) is the most prevalent in HPV-induced malignant diseases. The viral oncoproteins E6 and E7 are convenient targets for anti-tumor immunization. To adapt the corresponding genes for DNA vaccination, their oncogenicity needs to be reduced and immunogenicity enhanced. The main modifications for achieving these aims include mutagenesis, rearrangement of gene parts, and fusion with supportive cellular or viral/bacterial genes or their functional parts.
As HPVs are strictly human specific, an animal model of HPV infection does not exist. Therefore, immunization against HPV-induced tumors is most frequently tested in mouse models utilizing transplantable syngeneic tumor cells producing the HPV16 E6/E7 oncoproteins. In this chapter, one such cell line designated TC-1 is characterized and the effect of immunization with the modified E7 fusion gene against TC-1-induced subcutaneous tumors is described. As down-regulation of MHC class I molecules is one of the most important escape mechanisms of cervical carcinoma cells, the TC-1/A9 clone with reversibly reduced MHC class I expression has been developed and, herein, its response to DNA vaccination is also shown and compared with that of the TC-1 cells.
