EDA-E7 activated DCs induces specific cytotoxic T lymphocyte immune responses against HPV expressing cervical cancer in human setting

Abstract Background Cervical cancer is a major cause of cancer death in women worldwide. Human papillomavirus (HPV) infection especially genotypes 16 and 18 is the main factor induces cervical lesions. Targeting HPV viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing of HPV infected cervical cancer is of great potential benefit for cervical cancer treatment. Methods Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8 + T cells response in mouse. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as specific antitumor T cell response. Results We found that EDA-E7 could be efficiently captured by human PBMC derived dendritic cells (DCs) in vitro and induce DCs maturation. Importantly, this effect can work in synergy with the TLR ligand anti-CD40 agonist, polyinosinic-polycytidylic acid [poly (I:C)], R848 and CpG2216. EDA-E7 matured DCs could activate T cells and trigger anti-tumor response in vitro. Single RNA sequencing and T cell target killing assay confirmed the activation of T cells by EDA-E7 matured DCs. Conclusions Therapeutic vaccination with EDA-E7 fusion protein is effective for human cervical carcinoma treatment.