1. Academic Validation
  2. Adjuvant-free peptide vaccine targeting Clec9a on dendritic cells can induce robust antitumor immune response through Syk/IL-21 axis

Adjuvant-free peptide vaccine targeting Clec9a on dendritic cells can induce robust antitumor immune response through Syk/IL-21 axis

  • Theranostics. 2021 May 24;11(15):7308-7321. doi: 10.7150/thno.56406.
Shanshan Gou 1 Shuai Wang 1 Wenwen Liu 1 Guanyu Chen 2 Dongyang Zhang 1 Jiangfeng Du 1 Zhongyi Yan 1 Hongfei Wang 1 Wenjie Zhai 1 Xinghua Sui 2 Yahong Wu 1 Yuanming Qi 1 Yanfeng Gao 1 2
Affiliations

Affiliations

  • 1 School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 2 School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China.
Abstract

Dendritic cells (DCs) can process the antigens of Cancer vaccine and thus stimulate the CD8+ T cells to recognize and kill the tumor cells that express these antigens. However, lack of promising carriers for presenting the antigens to DCs is one of the main barriers to the development of clinically effective Cancer vaccines. Another limitation is the risk of inflammatory side effects induced by the adjuvants. It is still unclear how we can develop ideal adjuvant-free DC vaccine carriers without adjuvants. Methods: A 12-mer peptide carrier (CBP-12) with high affinity for Clec9a expressed on DCs was developed using an in silico rational optimization method. The therapeutic effects of the adjuvant-free vaccine comprising CBP-12 and exogenous or endogenous antigenic Peptides were investigated in terms of antigen cross-presentation efficacy, specific cytotoxic T lymphocyte response, and antitumor activity. We also explored the mechanism involved in the antitumor effects of the adjuvant-free CBP-12 vaccine. Finally, we assessed the effects of the CBP-12 conjugated peptide vaccine combined with radiotherapy. Results: Here, we developed CBP-12 as a vaccine carrier that enhanced the uptake and cross-presentation of the antigens, thus inducing strong CD8+ T cell responses and antitumor effects in both anti-PD-1-responsive (B16-OVA) and -resistant (B16) models, even in adjuvant-free conditions. CBP-12 bound to and activated Clec9a, thereby stimulating Clec9a+ DC to product IL-21, but not IL-12 by activating of Syk. The antitumor effects of the CBP-12 conjugated peptide vaccines could be blocked by an IL-21 neutralizing antibody. We also observed the synergistic antitumor effects of the CBP-12 conjugated peptide vaccine combined with radiotherapy. Conclusions: CBP-12 could serve as an adjuvant-free peptide vaccine carrier for Cancer Immunotherapy.

Keywords

Clec9a; IL-21; cancer immunotherapy; dendritic cell; peptide vaccine.

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