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Pharm Res. 2018 Mar 2;35(4):80. doi: 10.1007/s11095-018-2355-z.

CpG-PEG Conjugates and their Immune Modulating Effects after Systemic Administration.

Author information

1
Zhejiang-California International NanoSystems Institute, Zhejiang University, Hangzhou, China.
2
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
3
College of Pharmacy and Chemistry, Dali University, Dali, China. yhxu@sjtu.edu.cn.

Abstract

PURPOSE:

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs were found to be able to target cells that express Toll-like receptor 9 to modulate innate and adaptive immune reactions. But their in vivo application in immunotherapy against cancer has not been successful. We attempted in this study to examine polyethylene-glycol (PEG) conjugated CpG ODNs and investigated their mechanism of immune modulation in anti-cancer therapy.

METHODS:

CpG-PEG conjugates with different PEG lengths were synthesized. In vitro activity as well as in vivo pharmacokinetics and pharmacodynamics properties were evaluated.

RESULTS:

CpG-PEG20Ks were found to be able to persist longer in circulation and activate various downstream effector cells. After intravenous injection, they resulted in higher levels of IL-12p70 in the circulation and lower M-MDSC infiltrates in the tumor microenvironment. Such activities were different from those of CpG ODNs without PEGylation, suggesting different PK-PD profiles systemically and locally.

CONCLUSIONS:

Our data support the development of CpG-PEGs as a new therapeutic agent that can be systemically administered to modulate immune responses and the microenvironment in tumor tissues.

KEYWORDS:

CpG-ODN; PEG; immune modulation; systemic administation

PMID:
29500548
DOI:
10.1007/s11095-018-2355-z
[Indexed for MEDLINE]

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