THERAPEUTIC VACCINES FOR CERVICAL-CANCER - CONCEPT AND CLINICAL-RESULTS

Human papillomavirus (HPV) infection is associated with transformation and clonal expansion of infected epithelial cells, resulting in the p roduction of a benign growth, i.e. a wart. Recently, however, HPV hits emerged as the primary causative agent of cervical carcinoma, maligna ncy being associated with the presence of the viral genome (predominan tly genotypes 16 and 18) in cancerous cells. The only HPV proteins rel iably expressed in neoplastic lesions are the 'oncogenic' E6 and E7 pr oteins, that serve both as tumour-specific markers and potential targe ts for immunotherapeutic intervention. As intracellular (nuclear) prot eins, the E6 and E7 gene products may be hidden from the humoral immun e response. Attention has thus focused on the generation of a vaccine capable of inducing or stimulating a cellular immune response to HPV 1 6 and HPV 18 E6 and E7. Vaccine development has been constrained by th e absence of an appropriate animal model, the oncogenic nature of E6 a nd E7 and technical difficulties associated with detection of cytotoxi c T cell responses to these antigens. Despite these difficulties, vacc ine strategies have now been devised based on immunisation with synthe tic peptide, whole protein and a vaccinia virus recombinant. Phase I/I I human clinical trials have been initiated, and preliminary results h ave demonstrated the induction of specific cellular immune responses a fter immunisation. The HPV-associated neoplasia in cervical cancer rep resents an excellent target for therapeutic intervention because the t umour-associated antigens are so clearly defined. As such, it provides an appropriate model for establishing the general principles of cance r immunotherapy in humans.