Recently, professor Zhang Lifang’s research team from the School of Basic Medical Sciences published an article on Theranostics which proved that the human papillomaviruses HPV16E7 protein affibody and its affitoxin molecules are with high binding affinity and specificity and anti-cervical cancer function, which will be extremely promising on the molecular diagnosis and target treatment of HPV infected cervical cancer and head and neck cancers. Doctor Jiang Pengfei is the first author, and professor Zhang Lifang is the correspondent author. Theranostics is An1 journal with an impact factor of 9.009 averagely in 5 years.
ZHPV16E7 affibody and affitoxin384 showed target binding affinity in tumor-bearing nude mouse models.
HPV16 is the most common genotype associated with the infection of cervical cancer and head and neck cancers. The E7 protein encoded by the early region (E) of the HPV gene is a oncogenic protein of HPV-induced cancer. It is persistently and steadily over expressed in cancer and its precancerous lesions, but does not exist in normal tissues, therefore, it is a very specific target antigen for the molecular diagnosis and treatment research of HPV related cancers. Although HPV L1-based cervical cancer preventive vaccines have been commercialized and have been shown to be effective in preventing HPV infection and cervical cancer caused by HPV infection, they have no therapeutic effect on cervical cancer and some head and neck cancers that have been infected or have occurred. To date, HPV-based therapeutic vaccines or targeted therapeutic agents for cervical cancer have not been commercialized. Therefore, it is urgent to do research and development on these vaccines.
Professor Zhang Lifang’s team has long been doing research on the pathogenesis, prevention and treatment of HPV and cervical cancer. Based on the technology and platform established in the laboratory, the team has screened affibody, a small peptide with high affinity to HPV16 E7. The research found that affibody molecules bind to HPVE7 molecules with high affinity, and possess the characteristics of good tissue penetration, easy preparation and stability which are special advantages on the molecular imaging diagnosis and target therapy of cervical cancer. The team further utilized the target ability of ZHPV16E7 with Pseudomonas Exotoxin A (PE38KDEL) as cytotoxic molecules to construct an affibody/PE38KDEL prokaryotic expression recombinant. The affitoxin, ZHPV16E7 affitoxinT384 was generated by fusing the modified Pseudomonas Exotoxin A (PE38KDEL) to the HPV16 E7-specific affibody by a prokaryotic expression system. Through the test of protein level, cell level and the level of animal in vivo, it is proved that ZHPV16E7 affitoxin384 targeted HPV16 E7 with high binding affinity and specificity, and showed significant in vivo antitumor efficacy in tumor-bearing nude mouse models.
The article published by Trends Biotechnol, Affibody Molecules in Biotechnological and Medical Applications, reviews the research and points out that Z HPV16E7 affibody has great potential in molecular imaging diagnosis of cervical cancer.
Link of the article: https://www.ncbi.nlm.nih.gov/pubmed/30026865