Constitutive STAT3 signaling, in comparison to STAT5, enhances CAR T cell efficacy and lowers systemic toxicity - PubMed
5 hours ago
- #cancer immunotherapy
- #STAT3 signaling
- #CAR T cells
- Constitutive STAT3 signaling enhances CAR T cell efficacy and reduces systemic toxicity compared to STAT5.
- CAR T cells with constitutively active STAT3 (caSTAT3) showed enhanced effector function and a robust memory phenotype in vitro.
- caSTAT3 CAR T cells activated apoptosis-related genes, limiting their expansion in vitro but showed durable antitumor activity in vivo.
- caSTAT5 CAR T cells demonstrated sustained proliferation but caused lethal systemic toxicity due to infiltration into non-tumor tissues.
- Coexpression of caSTAT3 and caSTAT5 enhanced long-term proliferative capacity of CAR T cells, even without antigen stimulation.
- Selective activation of STAT3 at optimal levels may improve CAR T cell efficacy while minimizing off-tumor toxicities.