RGX-104 Hydrochloride

RGX-104 Hydrochlorideは経口活性の肝臓X受容体（LXR）作動剤であり、アポリポタンパク質E（ApoE）遺伝子の転写を活性化することで、先天性免疫を調節する^{[1, 2]}。ApoEの上方制御は、骨髄由来抑制細胞（MDSC）や制御性T細胞（Treg）などの免疫抑制細胞の排除を促進し、よって腫瘍微小環境の免疫抑制状態を逆転させ、抗腫瘍免疫反応を増強する^[3]。RGX-104 Hydrochlorideは、抗腫瘍活性をも示し、細胞のピロプトーシスを誘発する^{[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.