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Immunotherapy for Cervical Cancer

Research Status and Clinical Potential

Abstract

The high-risk types of human papillomavirus (HPV) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. Despite recent advances in preventive HPV vaccine development, such preventive vaccines are unlikely to reduce the prevalence of HPV infections within the next few years, due to their cost and limited availability in developing countries. Furthermore, preventive HPV vaccines may not be capable of treating established HPV infections and HPV-associated lesions, which account for high morbidity and mortality worldwide. Thus, it is important to develop therapeutic HPV vaccines for the control of existing HPV infection and associated malignancies. Therapeutic vaccines are quite different from preventive vaccines in that they require the generation of cell-mediated immunity, particularly T cell-mediated immunity, instead of the generation of neutralizing antibodies. The HPV-encoded early proteins, the E6 and E7 oncoproteins, form ideal targets for therapeutic HPV vaccines, since they are consistently expressed in HPV-associated cervical cancer and its precursor lesions and thus play crucial roles in the generation and maintenance of HPV-associated disease. Our review covers the various therapeutic HPV vaccines for cervical cancer, including live vector-based, peptide or protein-based, nucleic acid-based, and cell-based vaccines targeting the HPV E6 and/or E7 antigens. Furthermore, we review the studies using therapeutic HPV vaccines in combination with other therapeutic modalities and review the latest clinical trials on therapeutic HPV vaccines.

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Acknowledgments

This review is not intended to be an encyclopedic one, and the authors apologize to those not cited. We gratefully acknowledge Dr Richard Roden for his critical review of the manuscript. The work is supported by the NCI SPORE in Cervical Cancer P50 CA098252 and NCI 1RO1 CA114425-01.

The authors have no conflicts of interest that are directly relevant to the content of this review.

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Correspondence to Dr T.-C. Wu.

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Su, J., Wu, A., Scotney, E. et al. Immunotherapy for Cervical Cancer. BioDrugs 24, 109–129 (2010). https://doi.org/10.2165/11532810-000000000-00000

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Keywords

  • Cervical Cancer
  • Major Histocompatibility Complex Class
  • Cervical Intraepithelial Neoplasia
  • Venezuelan Equine Encephalitis Virus