Natural killer cell reprogramming with chimeric immune receptors

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. These methods are applicable to the reprogramming of NK cells with chimeric receptors specific for other antigens expressed on cancer cells as well as with molecules that can modulate NK cell function.