Pharmaceutical Research

, 35:80 | Cite as

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

  • Caixing Wu
  • Xiaofei Xiang
  • Yang Yue
  • Lin Li
  • Yesen Li
  • Chong Zhang
  • Yuhong Xu
Research Paper



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.


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


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.


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.

Key Words

CpG-ODN PEG immune modulation systemic administation 







Polyethylene glycol


PEG conjugated CpG ODNs




M type myeloid derived suppressor cells






Overall survival


Progression free survival








Toll-like receptor 9


CpG ODNs containing the sulfhydryl group


High performance liquid chromatography


Immunoglobulin G




Interferon gamma


Enzyme-linked immunosorbent assay


Bone-marrow-derived dendritic cells


A type I C-type lectin receptor that is expressed on various antigen presenting cell subsets


Phosphate-buffered saline


Quantitative- polymerase chain reaction


Enhanced permeability and retention




Triethylamine and acetic acid


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Zhejiang-California International NanoSystems InstituteZhejiang UniversityHangzhouChina
  2. 2.School of PharmacyShanghai Jiao Tong UniversityShanghaiChina
  3. 3.College of Pharmacy and ChemistryDali UniversityDaliChina

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