A novel dendritic cell targeting HPV16 E7 synthetic vaccine in combination with PD-L1 blockade elicits therapeutic antitumor immunity in mice

Zhida Liu; Hang Zhou; Wenjun Wang; Yang-Xin Fu; Mingzhao Zhu

doi:10.1080/2162402X.2016.1147641

A novel dendritic cell targeting HPV16 E7 synthetic vaccine in combination with PD-L1 blockade elicits therapeutic antitumor immunity in mice

Oncoimmunology. 2016 Mar 10;5(6):e1147641. doi: 10.1080/2162402X.2016.1147641. eCollection 2016 Jun.

Authors

Zhida Liu¹, Hang Zhou², Wenjun Wang², Yang-Xin Fu³, Mingzhao Zhu⁴

Affiliations

¹ Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, TX, USA.
² Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
³ Department of Pathology, University of Texas, Southwestern Medical Center , Dallas, TX, USA.
⁴ Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China.

Abstract

Human papilliomavirus (HPV) oncogene E7, essential for the transformation and maintenance of the malignancy of cervical cancer cells, represents an ideal tumor-specific antigen for vaccine development. However, due to the poor immunogenicity of E7 protein, an effective therapeutic E7 vaccine is still lacking. Dendritic cells (DCs) are probably the most potent antigen presenting cells for the induction of cytotoxic T lymphocyte (CTL) response, which is crucial for tumor control. In this study, we tested whether targeting the E7 antigen to DCs in vivo would elicit therapeutic antitumor CTL response. We generated the DEC205-specific single-chain variable fragment (scFv) and E7 long peptide fusion protein [scFv(DEC205)-E7] based on the novel method of protein assembly we recently developed. This fusion protein vaccine demonstrated highly efficient DC-targeting in vivo and elicited much stronger protective CTL response than non-DC-targeting control vaccine in naive mice. Furthermore, the scFv(DEC205)-E7 vaccine showed significant therapeutic antitumor response in TC-1 tumor bearing mice. Importantly, PD-L1 blockade further improved the therapeutic effect of the scFv(DEC205)-E7 vaccine. Thus, the current study suggests an efficient strategy for cervical cancer immunotherapy by combining the DC(DEC205)-targeting E7 vaccine and PD-L1 blockade.

Keywords: Cervical cancer; DEC205; HPV E7; PD-1; PD-L1; dendritic cell; therapeutic vaccine.

Publication types

Research Support, Non-U.S. Gov't