PMID- 34158852
OWN - NLM
STAT- MEDLINE
DCOM- 20210729
LR  - 20240402
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 11
IP  - 15
DP  - 2021
TI  - Adjuvant-free peptide vaccine targeting Clec9a on dendritic cells can induce 
      robust antitumor immune response through Syk/IL-21 axis.
PG  - 7308-7321
LID - 10.7150/thno.56406 [doi]
AB  - 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.
CI  - (c) The author(s).
FAU - Gou, Shanshan
AU  - Gou S
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Wang, Shuai
AU  - Wang S
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Liu, Wenwen
AU  - Liu W
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Chen, Guanyu
AU  - Chen G
AD  - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 
      518107, China.
FAU - Zhang, Dongyang
AU  - Zhang D
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Du, Jiangfeng
AU  - Du J
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Yan, Zhongyi
AU  - Yan Z
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Wang, Hongfei
AU  - Wang H
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Zhai, Wenjie
AU  - Zhai W
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Sui, Xinghua
AU  - Sui X
AD  - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 
      518107, China.
FAU - Wu, Yahong
AU  - Wu Y
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Qi, Yuanming
AU  - Qi Y
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
FAU - Gao, Yanfeng
AU  - Gao Y
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 
      518107, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210524
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Cancer Vaccines)
RN  - 0 (Clec9a protein, mouse)
RN  - 0 (Interleukins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Vaccines, Subunit)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (Syk protein, mouse)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Animals
MH  - *Cancer Vaccines/immunology/pharmacology
MH  - Dendritic Cells/*immunology
MH  - *Drug Delivery Systems
MH  - Female
MH  - Interleukins/genetics/*immunology
MH  - Lectins, C-Type/genetics/*immunology
MH  - Melanoma, Experimental/genetics/*immunology/therapy
MH  - Mice
MH  - Mice, Knockout
MH  - *Peptides/immunology/pharmacology
MH  - Receptors, Immunologic/genetics/*immunology
MH  - Signal Transduction/*drug effects/genetics/immunology
MH  - Syk Kinase/genetics/*immunology
MH  - Vaccines, Subunit/immunology/pharmacology
PMC - PMC8210616
OTO - NOTNLM
OT  - Clec9a
OT  - IL-21
OT  - cancer immunotherapy
OT  - dendritic cell
OT  - peptide vaccine
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2021/06/24 06:00
MHDA- 2021/07/30 06:00
PMCR- 2021/01/01
CRDT- 2021/06/23 07:19
PHST- 2020/11/25 00:00 [received]
PHST- 2021/05/02 00:00 [accepted]
PHST- 2021/06/23 07:19 [entrez]
PHST- 2021/06/24 06:00 [pubmed]
PHST- 2021/07/30 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - thnov11p7308 [pii]
AID - 10.7150/thno.56406 [doi]
PST - epublish
SO  - Theranostics. 2021 May 24;11(15):7308-7321. doi: 10.7150/thno.56406. eCollection 
      2021.