RGX-104 Hydrochloride is an orally active liver X receptor (LXR) agonist that modulates innate immunity by activating the transcription of the apolipoprotein E (ApoE) gene[1, 2]. Up-regulation of ApoE promotes the clearance of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), thereby reversing the immunosuppressive state of the tumor microenvironment and enhancing antitumor immune responses[3]. RGX-104 Hydrochloride also exhibits antitumor activity and induces cell pyroptosis[4, 5].
References:
[1] Tavazoie M F, Pollack I, Tanqueco R, et al. LXR/ApoE activation restricts innate immune suppression in cancer[J]. Cell, 2018, 172(4): 825-840. e18.
[2] Mita M, Mita A, Chmielowski B, et al. Abstract B001: A phase 1 trial of RGX-104, a first-in-class immunotherapy targeting the liver-X nuclear hormone receptor (LXR), in patients with refractory malignancies[J]. Molecular Cancer Therapeutics, 2018, 17(1_Supplement): B001-B001.
[3] Zhang J, Zhu X, Han L, et al. Cholesterol Metabolism-Mediated Immune Regulation and Cancer Immunotherapy[J]. Available at SSRN 4760648.
[4] Liang H, Shen X. LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells[J]. Biochemical and Biophysical Research Communications, 2020, 528(2): 330-335.
[5] Qiu W, Su W, Xu J, et al. Immunomodulatory‐Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy[J]. Advanced Healthcare Materials, 2022, 11(21): 2201233.
RGX-104 Hydrochloride是一种具口服活性的肝X受体（Liver X Receptor, LXR）激动剂，能够通过载脂蛋白E（ApoE）基因的转录激活调节先天免疫[1, 2]。ApoE的上调能够促进机体清除体内的免疫抑制性细胞，如髓源性抑制细胞（MDSCs）和调节性T细胞（Tregs），从而解除肿瘤微环境的免疫抑制状态，增强抗肿瘤免疫应答[3]。RGX-104 Hydrochloride具有抗肿瘤活性，能够引发细胞焦亡[4, 5]。