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Natural killer (NK) cells hold promise for improving the therapeutic potential of allogeneic hematopoietic transplantation, but their effectiveness is limited by inhibitory HLA types. We sought to overcome this intrinsic resistance by transducing CD56+CD3- NK cells with chimeric receptors directed against CD19, a molecule widely expressed by malignant B cells. An abundance of NK cells for transduction was secured by culturing peripheral blood mononucle
Natural killer (NK) cells are emerging as a new tool for cell therapy of cancer. However, some cancer subtypes are relatively resistant to NK cell cytotoxicity. Expression of anti-CD19 chimeric signaling receptors can enhance NK-cell reactivity against CD19+ leukemia and lymphoma cells. Here we describe a method to enforce expression of such receptors in human NK cells relying on electroporation of mRNA and compare it to retroviral transduction of cDNA
The advent of immunotherapies for cancer, and more recently of cellular immunotherapies, has substantially altered the treatment landscape. In hematological malignancies, complete response rates to CAR-T cells can exceed 80%. These responses are often durable in nature and have attracted considerable excitement and investment in the development of cell therapies for an expanded range of indications, particularly in solid tumors. The continued progress of cell therapies depends on overcoming k
Purpose: To develop new therapies for children with solid tumors, we tested the cytotoxicity of natural killer (NK) cells expanded by coculture with K562-mb15-41BBL cells. We sought to identify the most sensitive tumor subtypes, clarify the molecular interactions regulating cytotoxicity, and determine NK antitumor potential in vivo.
Experimental design: We tested in vitro cytotoxicity of expanded NK cells a
Viral infection of the liver is a major risk factor for hepatocellular carcinoma (HCC). Natural killer (NK) cells recognize virally infected and oncogenically transformed cells, suggesting a therapeutic role for NK-cell infusions in HCC. Using the K562-mb15-41BBL cell line as a stimulus, we obtained large numbers of activated NK cells from the peripheral blood of healthy donors. Expanded NK cells exerted remarkably high cytotoxicity against HCC cell li