title: TA-CIN, a vaccine incorporating a recombinant HPV fusion protein (HPV16 L2E6E7) for the potential treatment of HPV16-associated genital diseases.
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.
authors.affiliation: Cardiff University, HPV Research Laboratories, Section of Obstetrics & Gynaecology School of Medicine, Heath Park, Cardiff, CF14 4XN, UK. hibbittssj@cf.ac.uk
authors.forename: Sam
authors.initials: S
authors.lastname: Hibbitts
mesh_terms: D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D005831:Genital Diseases, Female / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D005832:Genital Diseases, Male / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins