Monocyte-Derived dendritic cells are able to induce an E6/E7- specific, HLA I-restricted, cytotoxic actvity

The adoptive transfer of cancer Ag-specific effector T cells in patients can result in tumor rejection, thereby illustrating the immune system potential for cancer therapy. For this point of view, viruses involved in tumorigenesis are useful targets because viral proteins are not expressed in normal cells and, generally, their expression is required to maintain the malignant phenotype. Between oncoviruses, human papillomavirus (HPV) has a well-characterized transforming propriety and it has been associated with squamous cell carcinoma of the ano-genital and oral tracts. In addition cutaneous genotypes are also associated with some forms of non-melanoma skin cancer. Transforming ability of HPV is based on the function of E6 and E7 viral oncoproteins, which interact and inactivate pRB and p53 oncosuppressors, respectively. For these reasons vaccines targeting oncogenic E6 and E7 are ideal candidates to elicit strong immune responses without generating autoimmunity. Here we report preliminary results obtained using a protocol based on human monocyte-derived dendritic cells (MDDC) incubated in vitro with apoptotic keratinocytes expressing both E6 and E7 oncoproteins derived from mucosal (HPV16) or cutaneous (HPV38) genotypes. We observed the capability of MDDCs i) to uptake apoptotic bodies from transformed keratinocytes; ii) to upregulate the expression of class I HLA and CD86 co-stimulatory molecule following apoptotic bodies uptake and iii) to specifically prime in vitro cytotoxic T lymphocytes against E6/E7-expressing keratinocytes. These findings indicate that this strategy could be a feasible immunotherapeutic approach for the treatment of established viral-induced tumors helping to launch more effective and less invasive therapeutic vaccines for HPV-mediated malignancies.