Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSC)—an immunosuppressive innate cell population. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients. So it is a target for enhancing efficacy of cancer immunotherapy in patients. RGX104 Free Acid is a potent LXRβ agonist. Oral administration of RGX-104 (100 mg/kg) to animals bearing palpable tumors significantly suppressed the growth of multiple cancer types. Co-administration of RGX-104 (100 mg/kg) and anti-PD-1 therapy in the Lewis lung cancer model was well tolerated and yielded synergistic anti-tumor activity in the absence of adjuvant tumor antigen vaccination. Monocytic-MDSCs (CD14+LinnegHLA-DRlow) also exhibited reduced abundance 2–3 weeks after RGX-104 treatment initiation relative to pre-dose levels in 5 of 6 patients. RGX-104 is currently in an ongoing multicenter dose escalation phase 1 trial in patients with metastatic solid cancers or lymphomas[1]. PAH/RGX-104@PDM/PTX (a dual-pH-sensitivity conjugated micelle system) exhibits superior tumor accumulation as well as tumor penetration, and suppresses 74.88% in vivo tumor growth. More importantly, PAH/RGX-104@PDM/PTX has significantly alleviated tumor immunosuppression by eliminating MDSCs and increasing cytotoxic T lymphocytes infiltration[2].
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