CTLs from the peripheral blood mononuclear cells from a cervi cal cancer patient following immunization with a recombinant vaccinia using in vitro restimulation with adenovirus recombinants expressing HPV16 or HPV1S E6/E7 fusion

Human papillomaviruses (HIPVs), especially types 16 and 18, are strongly associated with the development of cervical intraepithelial neo. plasia(CIN)and Invasivecarcinoma.The HPV E6 and E7 proteinsare expressed constitutively in the majority of CIN lesions and carcinomas. Therefore, they are targets for the inunune response against HPV and candidates for active immunotherapy. We have previously detected HPV specific CTLs from the peripheral blood mononuclear cells from a cervi cal cancer patient following immunization with a recombinant vaccinia using in vitro restimulation with adenovirus recombinants expressing HPV16 or HPV1S E6/E7 fusion proteins. In this study, we used a similar protocol to determine the prevalence of CTL responses against HPV16 andHPV18E6/E7Intheperipheralbloodmononuclearcellsfrom10CIN Ill and 10normalsubjects.HPV-speclflcCTLresponsesweredetectedin 6 of 10 CIN III subjects. These CTL lines recognized HPV16 E61E7 proteins presented by at least three MHC class 1 HLA alleles and by HPV-transformedCaSkicells. No HPV-speciflcCTLs were detectedIn normal subjects. This study demonstrates the presence of naturally oc curling HPV-speclflc memory CTLs In a majority of CIN III patIents and provides an approach for further study of their role in modulating cer vical malignancy.