Yan Leyfman, Medical Oncologist, Co-Founder and Executive Director of MedNews Week, shared a post on LinkedIn հighlighted an article published in Nature Communications:
“Advancing ‘off-the-shelf’ cell therapies!
Allogeneic cellular immunotherapy holds great promise for cancer treatment, but donor cell rejection remains a key challenge. A new study systematically evaluated immune barriers — including HLA, PD-L1, HLA-E, and CD47 — and identified CD8⁺ T cells as the dominant mediators of allorejection. Researchers developed a single-gene construct combining:
- shRNA to selectively silence HLA class I (but preserve HLA-E)
- a chimeric antigen receptor (CAR)
- PD-L1 or single-chain HLA-E (SCE)
This innovation enables CAR-NK cells to:
- Evade host rejection in vitro and in vivo
- Sustain potent anti-tumor activity
- Reduce exhaustion and cytokine release
These findings mark a major step toward safe, effective, ‘off-the-shelf’ allogeneic CAR-NK therapies for cancer.”
Title: Selective HLA knockdown and PD-L1 expression prevent allogeneic CAR-NK cell rejection and enhance safety and anti-tumor responses in xenograft mice
Authors: Fuguo Liu, Mubin Tarannum, Yingjie Zhao, Yiming Zhang, James Ham, Kewen Lei, Yuhao Qiang, Xingyu Deng, Maily Nguyen, Khanhlinh Dinh, Shaobo Yang, Alaa Kassim Ali, Toni Choueiri, Jerome Ritz, Rizwan Romee, Jianzhu Chen
Read the Full Article.
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