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Toll-Like Receptor 9 Agonists for Cancer Therapy

1
Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, University of Verona, 10, Piazzale L.A. Scuro, 37134 Verona, Italy
2
Medical Oncology, Azienda Ospedaliera Universitaria Integrata, 10, Piazzale L.A. Scuro, 37134 Verona, Italy
3
Laboratory of Oncology and Molecular Therapy, Department of Medicine, University of Verona, 10, Piazzale L.A. Scuro, 37134 Verona, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2014, 2(3), 211-228; https://doi.org/10.3390/biomedicines2030211
Received: 17 April 2014 / Revised: 24 July 2014 / Accepted: 28 July 2014 / Published: 4 August 2014
(This article belongs to the Special Issue Gene Therapy Used in Cancer Treatment)
The immune system has acquired increasing importance as a key player in cancer maintenance and growth. Thus, modulating anti-tumor immune mediators has become an attractive strategy for cancer treatment. Toll-like receptors (TLRs) have gradually emerged as potential targets of newer immunotherapies. TLR-9 is preferentially expressed on endosome membranes of B-cells and plasmacytoid dendritic cells (pDC) and is known for its ability to stimulate specific immune reactions through the activation of inflammation-like innate responses. Several synthetic CpG oligonucleotides (ODNs) have been developed as TLR-9 agonists with the aim of enhancing cancer immune surveillance. In many preclinical models, CpG ODNs were found to suppress tumor growth and proliferation both in monotherapy and in addition to chemotherapies or target therapies. TLR-9 agonists have been also tested in several clinical trials in patients with solid tumors. These agents showed good tolerability and usually met activity endpoints in early phase trials. However, they have not yet been demonstrated to significantly impact survival, neither as single agent treatments, nor in combination with chemotherapies or cancer vaccines. Further investigations in larger prospective studies are required. View Full-Text
Keywords: TLR-9; CpG ODN; immune modulatory oligonucleotides; PF-3512676 TLR-9; CpG ODN; immune modulatory oligonucleotides; PF-3512676
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MDPI and ACS Style

Melisi, D.; Frizziero, M.; Tamburrino, A.; Zanotto, M.; Carbone, C.; Piro, G.; Tortora, G. Toll-Like Receptor 9 Agonists for Cancer Therapy. Biomedicines 2014, 2, 211-228. https://doi.org/10.3390/biomedicines2030211

AMA Style

Melisi D, Frizziero M, Tamburrino A, Zanotto M, Carbone C, Piro G, Tortora G. Toll-Like Receptor 9 Agonists for Cancer Therapy. Biomedicines. 2014; 2(3):211-228. https://doi.org/10.3390/biomedicines2030211

Chicago/Turabian Style

Melisi, Davide, Melissa Frizziero, Anna Tamburrino, Marco Zanotto, Carmine Carbone, Geny Piro, and Giampaolo Tortora. 2014. "Toll-Like Receptor 9 Agonists for Cancer Therapy" Biomedicines 2, no. 3: 211-228. https://doi.org/10.3390/biomedicines2030211

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