Significant growth inhibition by a bispecific affibody targeting oncoprotein E7 in both HPV16 and 18 positive cervical cancer in vitro and in vivo

Abstract

The infection with HPV 16 and 18 high-risk types account for more than 80 % of cervical cancer incidence, but there is still no targeted agent against HPV for cervical cancer therapy. Our previous study constructed a bispecific affibody Z16-18 targeting HPV16 and 18 early antigen 7 (E7, responsible for the infected cell malignant transformation). In the present study, we prepared Z16-18 in prokaryotic expression system and confirmed its significant growth inhibition both on SiHa (HPV16 positive) and HeLa (HPV18 positive) cervical cancer cells by arresting cell cycle at G0/G1 phase. The IC50 of Z16-18 on SiHa and HeLa were close in value. Z16-18 could specifically target E7 in both SiHa and HeLa, and exhibited prominent targeted enrichment on tumor tissues derived from SiHa or HeLa, resulting in the inhibition of tumourigenesis and tumour growth in vivo. Furthermore, Z16-18 could inhibit the interaction between E7 and pRb to block the E7-pRb carcinogenic pathway, resulting in the decreased release of E2F and the cell growth inhibition characterized by the decrease of CDK6 and Cyclin D1. This study provides a new strategy for targeted therapy based on affibody, and Z16-18 has great potential for utilisation and development as an agent targeting HPV16 and HPV18 related cervical cancer.