E6E7融合蛋白联合免疫刺激复合物（ISCOMATRIX）佐剂用于宫颈上皮内瘤变女性的HPV16特异性免疫疗法的1期研究。

Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX adjuvant in women with cervical intraepithelial neoplasia.

作者信息

Frazer Ian H, Quinn Michael, Nicklin Jim L, Tan Jeffrey, Perrin Lew C, Ng Peng, O'Connor Vivienne M, White Olivia, Wendt Ngaire, Martin Juliet, Crowley Jayne M, Edwards Stirling J, McKenzie Andrew W, Mitchell Susan V, Maher Darryl W, Pearse Martin J, Basser Russell L

机构信息

Centre for Immunology and Cancer Research, The University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia.

出版信息

Vaccine. 2004 Nov 25;23(2):172-81. doi: 10.1016/j.vaccine.2004.05.013.

DOI:10.1016/j.vaccine.2004.05.013

PMID:15531034

Abstract

PURPOSE

Persistent infection of cervical epithelium with "high risk" human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX adjuvant (HPV16 Immunotherapeutic) for patients with CIN.

EXPERIMENTAL DESIGN

Patients with CIN (n = 31) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy.

RESULTS

Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients.

CONCLUSIONS

The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX adjuvant is safe and induces vaccine antigen specific cell mediated immunity.

摘要