Therapeutic Vaccines for Cervical Cancer: Dendritic Cell-Based Immunotherapy

A.   D.   Santin; S.      Bellone; J.   J.   Roman; A.      Burnett; M.   J.   Cannon; S.      Pecorelli

Abstract

Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical dysplasia and cervical cancer. Several lines of evidence suggest that cell-mediated immune responses are important in controlling both HPV infections and HPV-associated neoplasia. Since HPV E6 and E7 oncoproteins are expressed in these lesions and are necessary for the maintenance of the malignant phenotype, these proteins might be potential tumor-specific target antigens for immunotherapy of cervical cancer. The gold standard treatment for locally advanced cervical cancer is primary radiation therapy combined with chemotherapy. A potential drawback of this potentially curative treatment is a profound and long lasting negative effect on the immune system. Treatment-induced immunosuppression combined with tumor-induced subversion of the immune system may therefore impose severe limitations on the efficacy of conventional vaccination strategies in late stage cervical cancer patients. The recognition of dendritic cells (DC) as powerful antigen-presenting cells capable of inducing primary T cell responses in vitro and in vivo, has recently generated widespread interest in DC-based immunotherapy of several human malignancies. Here, we review various therapeutic HPV vaccines being developed and implemented in human clinical trials, with a particular emphasis on the use of autologous DC pulsed with full-length HPV 16 or 18 E7 oncoproteins as a novel strategy to induce HPV E7-specific and tumor-specific T cell responses in cervical cancer patients following conventional treatment.

Keywords: human papillomavirus, dendritic cells, cervical cancer, cytotoxic t lymphocytes, immunotherapy, immunosuppression

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