PMID- 32231003
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 4
DP  - 2020 Mar 28
TI  - Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate 
      Tumor Microenvironment through Dendritic Cells.
LID - 10.3390/cancers12040810 [doi]
LID - 810
AB  - Dendritic cells (DCs) are antigen-presenting cells involved in T cell activation 
      and differentiation to regulate immune responses. Lipoimmunogens can be developed 
      as pharmaceutical lipoproteins for cancer immunotherapy to target DCs via 
      toll-like receptor 2 (TLR2) signaling. Previously, we constructed a 
      lipoimmunogen, a lipidated human papillomavirus (HPV) E7 inactive mutant 
      (rlipoE7m), to inhibit the growth of HPV16 E7-expressing tumor cells in a murine 
      model. Moreover, this antitumor effect could be enhanced by a combinatory 
      treatment with CpG oligodeoxynucleotides (ODN). To improve safety, we developed a 
      rlipoE7m plus DOTAP liposome-encapsulated native phosphodiester CpG (POCpG/DOTAP) 
      treatment to target DCs to enhance antitumor immunity. We optimized the 
      formulation of rlipoE7m and POCpG/DOTAP liposomes to promote conventional DC and 
      plasmacytoid DC maturation in vitro and in vivo. Combination of rlipoE7m plus 
      POCpG/DOTAP could activate conventional DCs and plasmacytoid DCs to augment IL-12 
      production to promote antitumor responses by intravenous injection. In addition, 
      the combination of rlipoE7m plus POCpG/DOTAP could elicit robust cytotoxic T 
      lymphocytes (CTLs) by intravenous immunization. Interestingly, the combination of 
      rlipoE7m plus POCpG/DOTAP could efficiently inhibit tumor growth via intravenous 
      immunization. Moreover, rlipoE7m plus POCpG/DOTAP combined reduced the number of 
      tumor-infiltrating regulatory T cells dramatically due to downregulation of IL-10 
      production by DCs. These results showed that the combination of rlipoE7m plus 
      POCpG/DOTAP could target DCs via intravenous delivery to enhance antitumor 
      immunity and reduce the number of immunosuppressive cells in the tumor 
      microenvironment.
FAU - Shen, Kuan-Yin
AU  - Shen KY
AUID- ORCID: 0000-0003-4326-2038
AD  - National Institute of Infectious Diseases and Vaccinology, National Health 
      Research Institutes, Miaoli 350401, Taiwan.
FAU - Liu, Hsin-Yu
AU  - Liu HY
AD  - National Institute of Infectious Diseases and Vaccinology, National Health 
      Research Institutes, Miaoli 350401, Taiwan.
FAU - Yan, Wan-Lun
AU  - Yan WL
AD  - National Institute of Infectious Diseases and Vaccinology, National Health 
      Research Institutes, Miaoli 350401, Taiwan.
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 
      114201, Taiwan.
FAU - Wu, Chiao-Chieh
AU  - Wu CC
AD  - National Institute of Infectious Diseases and Vaccinology, National Health 
      Research Institutes, Miaoli 350401, Taiwan.
FAU - Lee, Ming-Hui
AU  - Lee MH
AD  - National Institute of Infectious Diseases and Vaccinology, National Health 
      Research Institutes, Miaoli 350401, Taiwan.
FAU - Leng, Chih-Hsing
AU  - Leng CH
AD  - National Institute of Infectious Diseases and Vaccinology, National Health 
      Research Institutes, Miaoli 350401, Taiwan.
AD  - Graduate Institute of Biomedical Sciences, China Medical University, Taichung 
      404394, Taiwan.
FAU - Liu, Shih-Jen
AU  - Liu SJ
AD  - National Institute of Infectious Diseases and Vaccinology, National Health 
      Research Institutes, Miaoli 350401, Taiwan.
AD  - Graduate Institute of Biomedical Sciences, China Medical University, Taichung 
      404394, Taiwan.
AD  - Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807378, 
      Taiwan.
LA  - eng
GR  - MOST 106-2320-B-400 -016 -MY3/Ministry of Science and Technology/
GR  - IV-108-GP-02 and -03/National Health Research Institutes Flagship Grant/
GR  - V-108-PP16 and IV-108-SP-18/National Health Research Institutes intramural grant/
PT  - Journal Article
DEP - 20200328
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7225995
OTO - NOTNLM
OT  - DOTAP
OT  - Toll-like receptor 2
OT  - lipoprotein
OT  - liposome
OT  - phosphodiester CpG
COIS- The authors declare no conflict of interest.
EDAT- 2020/04/02 06:00
MHDA- 2020/04/02 06:01
PMCR- 2020/03/28
CRDT- 2020/04/02 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/03/23 00:00 [revised]
PHST- 2020/03/26 00:00 [accepted]
PHST- 2020/04/02 06:00 [entrez]
PHST- 2020/04/02 06:00 [pubmed]
PHST- 2020/04/02 06:01 [medline]
PHST- 2020/03/28 00:00 [pmc-release]
AID - cancers12040810 [pii]
AID - cancers-12-00810 [pii]
AID - 10.3390/cancers12040810 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Mar 28;12(4):810. doi: 10.3390/cancers12040810.