Nexavant was reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. The distinctive characteristics of Nexavant compared to that of Poly(I:C) were demonstrated by precise quantification, enhanced thermostability, and increased resistance to RNase A. Unlike Poly(I:C), which activates TLR3, RIG-I, and MDA5, Nexavant stimulates signaling through TLR3 and RIG-I but not through MDA5. Compared to Poly(I:C), an intratumoral Nexavant treatment led to a unique immune response, immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 antibody treatment in all the tested models and showed a synergistic effect in combinational therapy, especially in well-defined cold tumor models. The effect was similar to that of nivolumab in a humanized mouse model. Intranasal instillation of Nexavant led to the recruitment of immune cells (NK, CD4+ T, and CD8+ T) to the lungs, suppressing lung metastasis and improving animal survival. Our study highlighted Nexavant’s defined nature for clinical use and unique signaling pathways and its potential as a standalone anti-cancer agent or in combination with anti-PD-1 antibodies.
据报道，Nexavant可作为Poly(I:C)及其衍生物等TLR3激动剂的替代物。本研究对Nexavant的理化性质、信号通路、抗癌效应及其作用机制进行了系统探究。通过精确定量分析、增强的热稳定性及对RNase A耐受性的提升，证明了Nexavant相较于Poly(I:C)的独特性质。与可激活TLR3、RIG-I和MDA5的Poly(I:C)不同，Nexavant仅通过TLR3和RIG-I通路激活信号传导，而不通过MDA5。在多种动物癌症模型中，瘤内注射Nexavant能引发独特的免疫应答、促进免疫细胞浸润并抑制肿瘤生长，其效果优于Poly(I:C)。在所有测试模型中，Nexavant疗法均优于抗PD-1抗体治疗，并在联合治疗中显示出协同效应，尤其在典型冷肿瘤模型中效果显著。在人源化小鼠模型中，其疗效与纳武利尤单抗相当。鼻腔滴注Nexavant可募集免疫细胞（NK细胞、CD4+ T细胞和CD8+ T细胞）至肺部，抑制肺转移并提高动物存活率。本研究揭示了Nexavant明确的临床适用特性及其独特的信号通路机制，证明了其作为独立抗癌药物或与抗PD-1抗体联用的应用潜力。
肿瘤(癌症)患者之家