Gardiquimod is a Toll-like receptor 7 (TLR7) agonist that inhibits HIV-1 infection of human macrophages and activation of T cells[1, 2]. When combined with plant-derived norovirus virus-like particles (NVVLPs) and administered intranasally, Gardiquimod induces NVVLP-specific serum IgG and its subtype responses and mucosal IgA responses in the gastrointestinal, respiratory, and reproductive tracts[3].
In vitro, treatment of mouse spleen cells with Gardiquimod (0-2.5µg/mL) for 48h significantly induced cell proliferation[4]. Treatment of RAW264.7 mouse macrophages with Gardiquimod (1µg/mL) for 24h significantly induced the expression of CD40, CD80, and CD86[4]. Pretreatment of HaCaT cells with Gardiquimod (2µg/mL) for 2h downregulated the expression of Ca2+-induced differentiation markers and activated the Raf-MEK-ERK and PI3K-AKT signaling pathways in HaCaT cells[5]. Gardiquimod (3µg/mL) treatment of the human pancreatic adenocarcinoma cell line BxPC-3 inhibited cell proliferation and migration, induced apoptosis, downregulated the expression levels of cyclin B1, cyclin E, and B-cell lymphoma 2, and upregulated the expression of B-cell-associated X protein[6].
In vivo, subcutaneous B16 melanoma model mice treated with Gardiquimod (1mg/kg) via peritumoral injection twice, combined with a dendritic cell (DC) vaccine, significantly inhibited tumor growth[4].
References:
[1] Buitendijk M, Eszterhas S K, Howell A L. Gardiquimod: a Toll-like receptor-7 agonist that inhibits HIV type 1 infection of human macrophages and activated T cells[J]. AIDS research and human retroviruses, 2013, 29(6): 907-918.
[2] Goyal D K, Keshav P, Kaur S. Adjuvant effects of TLR agonist gardiquimod admixed with Leishmania vaccine in mice model of visceral leishmaniasis[J]. Infection, Genetics and Evolution, 2021, 93: 104947.
[3] Velasquez L S, Hjelm B E, Arntzen C J, et al. An intranasally delivered Toll-like receptor 7 agonist elicits robust systemic and mucosal responses to Norwalk virus-like particles[J]. Clinical and Vaccine Immunology, 2010, 17(12): 1850-1858.
[4] Ma F, Zhang J, Zhang J, et al. The TLR7 agonists imiquimod and gardiquimod improve DC-based immunotherapy for melanoma in mice[J]. Cellular & molecular immunology, 2010, 7(5): 381-388.
[5] Jia B, Luo X, Cheng F W, et al. Gardiquimod inhibits the expression of calcium-induced differentiation markers in HaCaT cells[J]. Molecular biology reports, 2013, 40(11): 6363-6369.
[6] Zou B B, Wang F, Li L, et al. Activation of Toll-like receptor 7 inhibits the proliferation and migration, and induces the apoptosis of pancreatic cancer cells[J]. Molecular medicine reports, 2015, 12(4): 6079-6085.
Gardiquimod是一种Toll样受体7（TLR7）激动剂，能够抑制HIV1型感染人类巨噬细胞和活化T细胞[1, 2]。Gardiquimod与植物源诺如病毒病毒样颗粒（NV VLPs）联合鼻内给药时，能够诱导胃肠道、呼吸道和生殖道产生NV VLP特异性血清IgG及其亚型应答和黏膜IgA应答[3]。
在体外，Gardiquimod（0-2.5µg/mL）处理小鼠脾细胞48h，显著诱导了细胞增殖[4]。Gardiquimod（1µg/mL）处理RAW264.7小鼠巨噬细胞24h，显著诱导了CD40、CD80和CD86的表达[4]。Gardiquimod（2µg/mL）预处理HaCaT细胞2h，下调了Ca2+诱导的分化标志物表达，激活了HaCaT细胞中的 Raf-MEK-ERK和PI3K-AKT信号通路[5]。Gardiquimod（3µg/mL）处理人胰腺腺癌细胞系BxPC-3细胞，抑制了细胞增殖和迁移，诱导了细胞凋亡，下调了细胞周期蛋白B1、细胞周期蛋白E和B细胞淋巴瘤2的表达水平，上调了B细胞相关X蛋白的表达[6]。
在体内，Gardiquimod（1mg/kg）通过肿瘤周围注射给药治疗皮下B16黑色素瘤模型小鼠2次，联合树突状细胞（DC）疫苗可显著抑制肿瘤的生长[4]。