Mezigdomide reverses T-cell exhaustion through degradation of IKZF1/IKZF3 and reinvigoration of cytokine production pathways - PubMed
2 hours ago
- #T-cell exhaustion
- #cereblon modulator
- #multiple myeloma
- Mezigdomide is a cereblon E3 ligase modulator that degrades IKZF1 and IKZF3, reversing T-cell exhaustion.
- IKZF1 and IKZF3 are critical regulators of T-cell exhaustion, binding to promoters and enhancers to alter transcription of exhaustion and cytokine genes.
- Treatment with mezigdomide decreases exhaustion markers, increases proinflammatory cytokine expression, and enhances killing with T-cell engagers like Alnuctamab in multiple myeloma.
- The study supports combining mezigdomide with T-cell engagers to improve therapeutic outcomes in multiple myeloma.