TA-CIN, a vaccine incorporating a recombinant HPV fusion protein (HPV16 L2E6E7) for the potential treatment of HPV16-associated genital diseases

Curr Opin Mol Ther. 2010 Oct;12(5):598-606.

Abstract

Commercially available prophylactic HPV vaccines for cervical cancer prevention have limited use in women with previous viral exposure. Therefore, a therapeutic HPV vaccine would benefit patients with HPV-associated genital diseases. Being developed by Cancer Research Technology Ltd, under license from Xenova Group plc, TA-CIN (Tissue Antigen - Cervical Intraepithelial Neoplasia) is a fusion protein vaccine comprising the HPV16 viral proteins L2, E6 and E7 for the treatment of HPV16-associated genital diseases. In mouse models, TA-CIN induced dose-dependent HPV16-specific CD4 and CD8 T-cell responses, which were enhanced when boosted with the vaccinia-based vector vaccine TA-HPV (Therapeutic Antigen - HPV). A phase I clinical trial of TA-CIN in healthy volunteers reported no serious adverse events and HPV16-specific cellular immune responses. Phase II trials in patients with anogenital and vulval intraepithelial neoplasia investigated heterologous prime/boost strategies with TA-CIN/TA-HPV and TA-HPV/TA-CIN, but neither of the regimens offered advantages over single-agent TA-HPV. A recent phase II trial investigating imiquimod/TA-CIN in patients with vulval intraepithelial neoplasia demonstrated significant infiltration of CD4 and CD8 T-cells in lesion responders and complete lesion regression in 63% of patients. More comprehensive case-controlled trials are needed to define responders to immunotherapy with TA-CIN and verify its prophylactic and therapeutic properties.

MeSH terms

  • Animals
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Female
  • Genital Diseases, Female / drug therapy*
  • Genital Diseases, Female / immunology
  • Genital Diseases, Female / virology*
  • Genital Diseases, Male / drug therapy*
  • Genital Diseases, Male / immunology
  • Genital Diseases, Male / virology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / adverse effects
  • Papillomavirus Vaccines / genetics
  • Papillomavirus Vaccines / metabolism
  • Papillomavirus Vaccines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / therapeutic use*

Substances

  • Papillomavirus Vaccines
  • Recombinant Fusion Proteins