Phase I/II Study of CD5 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Hematological Malignances

To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.

开始日期2024-04-22

申办/合作机构

The University of Texas MD Anderson Cancer Center

100 项与 CAR.5/IL15-transduced CB-NK cells(M.D. Anderson Cancer Center) 相关的临床结果

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100 项与 CAR.5/IL15-transduced CB-NK cells(M.D. Anderson Cancer Center) 相关的转化医学

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100 项与 CAR.5/IL15-transduced CB-NK cells(M.D. Anderson Cancer Center) 相关的专利（医药）

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项与 CAR.5/IL15-transduced CB-NK cells(M.D. Anderson Cancer Center) 相关的文献（医药）

2018-02-01·Leukemia1区 · 医学

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity

1区 · 医学

Article

作者: Liu, E ; Cai, R ; Marin, D ; Mukherjee, M ; Li, L ; Rezvani, K ; Bdaiwi, M H ; Savoldo, B ; Dotti, G ; Shpall, E ; Champlin, R ; Wierda, W ; Basar, R ; Muftuoglu, M ; Keating, M ; Gagea, M ; Banerjee, P ; Wan, X ; Reynolds, A ; Shaim, H ; Lu, X ; Tong, Y ; Orange, J

Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.

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