TLR3 Agonists: RGC100, ARNAX, and Poly-IC: a Comparative Review

Overview

Journal Immunol Res

Specialty Allergy & Immunology

Date 2021 Jun 19

PMID 34145551

Citations 22

Authors

Asma Komal

Mamoona Noreen

Attalla F El-Kott

Affiliations

Soon will be listed here.

Abstract

Toll-like receptors 3 (TLR3) have been broadly studied among all TLRs over the last few decades together with its agonists due to their contribution to cancer regression. These agonists undeniably have some shared characteristics such as mimicking dsRNA but pathways through which they exhibit antitumor properties are relatively diverse. In this review, three widely studied agonists RGC100, ARNAX, and poly-IC are discussed along with their structural and physiochemical differences including the signaling cascades through which they exert their actions. Comparison has been made to identify the finest agonist with maximum effectivity and the least side effect profile.

Citing Articles

Tumor cell membrane-based vaccines: A potential boost for cancer immunotherapy.

Yang M, Zhou J, Lu L, Deng D, Huang J, Tang Z Exploration (Beijing). 2024; 4(6):20230171.

PMID: 39713208 PMC: 11655317. DOI: 10.1002/EXP.20230171.

Exploiting the Zebrafish Model for Sepsis Research: Insights into Pathophysiology and Therapeutic Potentials.

He J, Xu P, Chen R, Chen M, Wang B, Xie Y Drug Des Devel Ther. 2024; 18:5333-5349.

PMID: 39600867 PMC: 11590671. DOI: 10.2147/DDDT.S500276.

Consensus, debate, and prospective on pancreatic cancer treatments.

Wang J, Yang J, Narang A, He J, Wolfgang C, Li K J Hematol Oncol. 2024; 17(1):92.

PMID: 39390609 PMC: 11468220. DOI: 10.1186/s13045-024-01613-x.

Poly I:C vaccination drives transient CXCL9 expression near B cell follicles in the lymph node through type-I and type-II interferon signaling.

Ball A, Morgaenko K, Anbaei P, Ewald S, Pompano R Cytokine. 2024; 183:156731.

PMID: 39168064 PMC: 11428038. DOI: 10.1016/j.cyto.2024.156731.

Interferon-stimulated gene 56 positively regulates Toll-like receptor 3-mediated CXCL10 expression in human renal proximal tubular epithelial cells.

Tachizaki M, Sakamoto S, Kobori Y, Asano Y, Kawaguchi S, Seya K FEBS Open Bio. 2024; 14(8):1303-1319.

PMID: 38923445 PMC: 11301256. DOI: 10.1002/2211-5463.13851.

References

Kang J, Demaria S, Formenti S . Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer. 2016; 4:51. PMC: 5028964. DOI: 10.1186/s40425-016-0156-7. View

Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K . Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med. 2008; 205(7):1601-10. PMC: 2442638. DOI: 10.1084/jem.20080091. View

Shime H, Maruyama A, Yoshida S, Takeda Y, Matsumoto M, Seya T . Toll-like receptor 2 ligand and interferon-γ suppress anti-tumor T cell responses by enhancing the immunosuppressive activity of monocytic myeloid-derived suppressor cells. Oncoimmunology. 2018; 7(1):e1373231. PMC: 5739553. DOI: 10.1080/2162402X.2017.1373231. View

Besch R, Poeck H, Hohenauer T, Senft D, Hacker G, Berking C . Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest. 2009; 119(8):2399-411. PMC: 2719920. DOI: 10.1172/JCI37155. View

Abe Y, Fujii K, Nagata N, Takeuchi O, Akira S, Oshiumi H . The toll-like receptor 3-mediated antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice. J Virol. 2011; 86(1):185-94. PMC: 3255933. DOI: 10.1128/JVI.05245-11. View

Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K . Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006; 441(7089):101-5. DOI: 10.1038/nature04734. View

Martins K, Bavari S, Salazar A . Vaccine adjuvant uses of poly-IC and derivatives. Expert Rev Vaccines. 2014; 14(3):447-59. DOI: 10.1586/14760584.2015.966085. View

Matsumoto M, Takeda Y, Tatematsu M, Seya T . Toll-Like Receptor 3 Signal in Dendritic Cells Benefits Cancer Immunotherapy. Front Immunol. 2018; 8:1897. PMC: 5742578. DOI: 10.3389/fimmu.2017.01897. View

Matsumoto M, Funami K, Tanabe M, Oshiumi H, Shingai M, Seto Y . Subcellular localization of Toll-like receptor 3 in human dendritic cells. J Immunol. 2003; 171(6):3154-62. DOI: 10.4049/jimmunol.171.6.3154. View

10.

Dunne A, ONeill L . Adaptor usage and Toll-like receptor signaling specificity. FEBS Lett. 2005; 579(15):3330-5. DOI: 10.1016/j.febslet.2005.04.024. View

11.

Azuma M, Ebihara T, Oshiumi H, Matsumoto M, Seya T . Cross-priming for antitumor CTL induced by soluble Ag + polyI:C depends on the TICAM-1 pathway in mouse CD11c(+)/CD8α(+) dendritic cells. Oncoimmunology. 2012; 1(5):581-592. PMC: 3429562. DOI: 10.4161/onci.19893. View

12.

Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M . RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol. 2004; 5(5):503-7. DOI: 10.1038/ni1061. View

13.

Hammerich L, Marron T, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S . Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019; 25(5):814-824. DOI: 10.1038/s41591-019-0410-x. View

14.

Park H, Adamson L, Ha T, Mullen K, Hagen S, Nogueron A . Polyinosinic-polycytidylic acid is the most effective TLR adjuvant for SIV Gag protein-induced T cell responses in nonhuman primates. J Immunol. 2013; 190(8):4103-15. PMC: 3622154. DOI: 10.4049/jimmunol.1202958. View

15.

Johnsen I, Nguyen T, Ringdal M, Tryggestad A, Bakke O, Lien E . Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling. EMBO J. 2006; 25(14):3335-46. PMC: 1523188. DOI: 10.1038/sj.emboj.7601222. View

16.

Heinz S, Haehnel V, Karaghiosoff M, Schwarzfischer L, Muller M, Krause S . Species-specific regulation of Toll-like receptor 3 genes in men and mice. J Biol Chem. 2003; 278(24):21502-9. DOI: 10.1074/jbc.M301476200. View

17.

Yamashita M, Chattopadhyay S, Fensterl V, Saikia P, Wetzel J, Sen G . Epidermal growth factor receptor is essential for Toll-like receptor 3 signaling. Sci Signal. 2012; 5(233):ra50. PMC: 3431157. DOI: 10.1126/scisignal.2002581. View

18.

Seya T, Takeda Y, Takashima K, Yoshida S, Azuma M, Matsumoto M . Adjuvant immunotherapy for cancer: both dendritic cell-priming and check-point inhibitor blockade are required for immunotherapy. Proc Jpn Acad Ser B Phys Biol Sci. 2018; 94(3):153-160. PMC: 5909060. DOI: 10.2183/pjab.94.011. View

19.

Jimenez-Dalmaroni M, Gerswhin M, Adamopoulos I . The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review. Autoimmun Rev. 2015; 15(1):1-8. PMC: 4679489. DOI: 10.1016/j.autrev.2015.08.009. View

20.

Matsumoto M, Tatematsu M, Nishikawa F, Azuma M, Ishii N, Morii-Sakai A . Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo. Nat Commun. 2015; 6:6280. DOI: 10.1038/ncomms7280. View