More than 99% of
cervical cancers have been associated with human papillomaviruses (HPVs), particularly HPV type 16. The clear association between
HPV infection and
cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic
vaccines. Although the recently licensed preventive
HPV vaccine,
Gardasil, has been shown to be safe and capable of generating significant protection against specific HPV types, it does not have
therapeutic effect against established
HPV infections and HPV-associated lesions. Two HPV oncogenic
proteins, E6 and E7, are consistently co-expressed in HPV-expressing
cervical cancers and are important in the induction and maintenance of cellular transformation. Therefore,
immunotherapy targeting E6 and/or E7
proteins may provide an opportunity to prevent and treat HPV-associated cervical
malignancies. It has been established that T cell-mediated immunity is one of the most crucial components to defend against
HPV infections and HPV-associated lesions. Therefore, effective therapeutic
HPV vaccines should generate strong E6/E7-specific T cell-mediated immune responses.
DNA vaccines have emerged as an attractive approach for
antigen-specific T cell-mediated
immunotherapy to combat
cancers. Intradermal administration of
DNA vaccines via a gene gun represents an efficient way to deliver
DNA vaccines into professional antigen-presenting cells in vivo. Professional antigen-presenting cells, such as dendritic cells, are the most effective cells for priming
antigen-specific T cells. Using the gene gun delivery system, we tested several
DNA vaccines that employ intracellular targeting strategies for enhancing MHC class I and class II presentation of encoded model
antigen HPV-16 E7. Furthermore, we have developed a strategy to prolong the life of DCs to enhance
DNA vaccine potency. More recently, we have developed a strategy to generate
antigen-specific CD4(+) T cell immune responses to further enhance
DNA vaccine potency. The impressive pre- clinical data generated from our studies have led to several HPV
DNA vaccine clinical trials.