CD19 CAR engineered NK 92 cells are sufficient to overcome NK cell resistance in B cell malignancies
Many B cell acute and chronic leukaemias tend to be resistant to killing by natural killer (NK) cells. The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance. Here, we extend our previous observations on the resistance of malignant lymphoblasts to NK 92 cells, a continuously growing NK cell line, showing that anti CD19 CAR (aCD19 CAR) engineered NK 92 cells can regain significant cytotoxicity against CD19 positive leukaemic cell lines and primary leukaemia cells that are resistant to cytolytic activity of parental NK 92 cells. The 'first generation' CAR was generated from a scFv (CD19) antibody fragment, coupled to a flexible hinge region, the CD3z chain and a Myc tag and cloned into a retrovirus backbone. No difference in cytotoxic activity of NK 92 and transduced aCD19 CAR NK 92 cells towards CD19 negative targets was found. However, aCD19 CAR NK 92 cells specifically and efficiently lysed CD19 expressing B precursor leukaemia cell lines as well as lymphoblasts from leukaemia patients. Since NK 92 cells can be easily expanded to clinical grade numbers under current Good Manufactoring Practice (cGMP) conditions and its safety has been documented in several phase I clinical studies, treatment with CAR modified NK 92 should be considered a treatment option for patients with lymphoid malignancies.
Journal of cellular and molecular medicine