EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting
Juan Feng,
Yongliang Liu,
Na Zhuang,
Zixuan Chai,
Limei Liu,
Cheng Qian,
Jiatao Li,
Juanjuan Shan
Affiliations
Juan Feng
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Yongliang Liu
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Na Zhuang
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Zixuan Chai
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Limei Liu
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Cheng Qian
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Jiatao Li
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Juanjuan Shan
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
Cervical cancer is a major cause of cancer death in women worldwide. Targeting human papillomavirus (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. Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for Toll-like receptor 4 (TLR4), and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8+ T cells response in mice. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as antitumor T cell response. 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 could 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 an anti-tumor response in vitro. Single cell RNA sequencing and T cell targeted killing assay confirmed the activation of T cells by EDA-E7 matured DCs. Therefore, therapeutic vaccination with EDA-E7 fusion protein maybe effective for human cervical carcinoma treatment.