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  • Title: Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells.
    Author: Robbins Y, Greene S, Friedman J, Clavijo PE, Van Waes C, Fabian KP, Padget MR, Abdul Sater H, Lee JH, Soon-Shiong P, Gulley J, Schlom J, Hodge JW, Allen CT.
    Journal: Elife; 2020 Jul 07; 9():. PubMed ID: 32633234.
    Abstract:
    Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1-dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.
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