1. Academic Validation
  2. Cholesterol-modified DP7 enhances the effect of individualized cancer immunotherapy based on neoantigens

Cholesterol-modified DP7 enhances the effect of individualized cancer immunotherapy based on neoantigens

  • Biomaterials. 2020 May;241:119852. doi: 10.1016/j.biomaterials.2020.119852.
Rui Zhang 1 Lin Tang 1 Yaomei Tian 1 Xiao Ji 1 Qiuyue Hu 1 Bailing Zhou 1 Ding Zhenyu 2 Xu Heng 3 Li Yang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 2 Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • 3 Precision Medicine Center, State Key Laboratory of Biotherapy, and Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.
  • 4 State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: [email protected].
Abstract

Personalized Cancer vaccines based on neoantigens have become an important research direction in Cancer Immunotherapy. However, their therapeutic effects are limited by the efficiency of antigen uptake and presentation by antigen presenting cells. Here, the low-toxicity cholesterol-modified antimicrobial peptide (AMP) DP7 (DP7-C), which has dual functions as a carrier and an immune adjuvant, improved the dendritic cell (DC)-based vaccine efficacy. As a delivery carrier, DP7-C can efficiently delivery various antigen Peptides into 75-95% of DCs via caveolin- and clathrin-dependent pathways. As an immune adjuvant, DP7-C can induce DC maturation and proinflammatory cytokine release via the TLR2-MyD88-NF-κB pathway and effectively increase antigen presentation efficiency. In addition, DP7-C enhanced the efficacy of DC-based individualized Cancer Immunotherapy and achieved excellent antitumor effects on mouse tumor models using the OVA antigen Peptides and LL2-neoantigens. Excitingly, after DP7-C stimulation, the antigen uptake efficiency of monocytes-derived DCs (MoDCs) in patients with advanced lung Cancer increased from 14-40% to 88-98%, the presentation efficiency increased from approximately 15% to approximately 65%, and the proportion of mature MoDCs increased from approximately 20% to approximately 60%. These findings suggest that our approach may be a potentially alternative strategy to produce Cancer vaccines designed for individual patients.

Keywords

Antitumor; DP7-C; Dendritic cell; Neoantigen; Personalized immunotherapy.

Figures
Products