CD79A/CD40 intracellular domain uses a 4-1BB-like metabolic pathway driven by cholesterol biosynthesis - PubMed
a day ago
- #CAR-T therapy
- #cholesterol metabolism
- #hematologic malignancies
- CD79A/CD40 CAR-T cells show superior proliferation and antitumor efficacy compared to CD28-based or 4-1BB-based CAR-T cells.
- Transcriptomic analysis reveals CD79A/CD40 CAR-T cells share metabolic pathways with 4-1BB CAR-T cells, particularly in oxidative phosphorylation (OXPHOS) and T cell memory differentiation.
- CD79A/CD40 CAR-T cells exhibit enhanced glycolysis early post-stimulation, supporting rapid expansion, while maintaining OXPHOS for long-term survival.
- Cholesterol biosynthesis is upregulated in both CD79A/CD40 and 4-1BB CAR-T cells, with higher serum LDL cholesterol levels correlating with better CAR-T expansion in 4-1BB therapy patients.
- Targeting cholesterol metabolism may optimize CAR-T cell function, improving therapeutic outcomes in hematologic malignancies.