USP22 Inhibition Potentiates GPC3 Chimeric Antigen Receptor Macrophages Efficacy in Hepatocellular Carcinoma by Downregulating Tumor CD24 Expression - PubMed
2 hours ago
- #Immunotherapy
- #Cell therapy
- #Cancer research
- GPC3-targeted chimeric antigen receptor macrophages (CAR-M) specifically bind, phagocytose, and kill GPC3-positive hepatocellular carcinoma (HCC) cells in vitro.
- RNA sequencing and flow cytometry show a positive correlation between USP22 and CD24, suggesting USP22 inhibition may reduce CD24 expression to alleviate phagocytic suppression.
- Combining USP22 inhibitor with GPC3 CAR-M enhances tumor-killing capacity in a dose-dependent manner and reduces CD24 on tumor cells.
- The combination strategy significantly suppresses tumor growth in murine peritoneal and patient-derived xenograft (PDX) HCC models.
- Enhanced efficacy is consistent across CAR-M derived from THP-1, human monocyte-derived macrophages, and human pluripotent stem cells, indicating broad applicability.
- Preclinical evidence supports combining GPC3 CAR-M therapy with USP22 inhibition as a potential immunotherapy for HCC.