We have located links that may give you full text access.
Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer.
Molecular Therapy 2024 September 2
Chimeric antigen receptor (CAR)-T cell therapy has shown limited success in patients with solid tumors. Recent in vitro and in vivo data have shown that adrenoceptor beta-2 (ADRB2) is a novel checkpoint receptor that inhibits T cell-mediated anti-tumor responses. To inhibit ADRB2-mediated inhibitory signaling, we downregulated ADRB2 in CAR-T (shβ2 -CAR-T) cells via RNA interference, assessed different parameters, and compared them with conventional second-generation CAR-T cells. ADRB2 knockdown CAR-T cells exhibited enhanced cytotoxicity against prostate cancer cell lines in vitro, by increasing CD69, CD107a, GzmB, IFN-γ, T-bet, and GLUT-1. Additionally, ADRB2 deficiency led to improved proliferation, increased CD8/CD4 T cell ratio, and decreased apoptosis in CAR-T cells. shβ2 -CAR-T cells expressed more Bcl-2 and led to the generation of more significant proportions of T central memory cells. Finally, the ZAP-70/NF-κB signaling axis was shown to be responsible for the improved functions of novel CAR-T cells. In tumor-bearing mice, shβ2 -CAR-T cells performed better than conventional CAR-T cells in eradicating prostate tumors. The study provides the basis for future clinical and translational CAR-T cell research to focus on adrenergic stress-mediated challenges in the tumor microenvironment of stressed tumors.
Full text links
Related Resources
Trending Papers
Ten tips to manage oral anticoagulation in hemodialysis patients with atrial fibrillation.Clinical Kidney Journal 2024 October
New strategies for the treatment of hyperkalemia.European Journal of Internal Medicine 2024 November 2
Mixed Cardiogenic Shock: A Proposal for Standardized Classification, a Hemodynamic Definition, and Framework for Management.Circulation 2024 October 29
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app