4.4 Review

Recent advances in chimeric antigen receptor natural killer cell therapy for overcoming intractable hematological malignancies

Journal

HEMATOLOGICAL ONCOLOGY
Volume 39, Issue 1, Pages 11-19

Publisher

WILEY
DOI: 10.1002/hon.2802

Keywords

CAR-NK cell; cellular therapy; NK cell

Funding

  1. Ministry of Health, Labor and Welfare of Japan
  2. Mitsubishi Foundation

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CAR-NK cells, with potent anti-leukemia/lymphoma effects and better proliferative capacity, have shown promise as an off-the-shelf allogeneic cellular therapy for overcoming intractable hematological malignancies. The safety and efficacy of CAR-NK cells, particularly in HLA-mismatched allogeneic cord blood-derived CD19 CAR-NK cell therapy for CD19-positive hematological malignancies, have been reported but the durability of clinical effects remains to be clarified.
Natural killer (NK) cells have a potent cytotoxic activity against leukemia and lymphoma without recognition of human leukocyte antigen (HLA) molecules. Chimeric antigen receptor-engineered NK cells (CAR-NK cells) can be produced from the NK92 cell line, peripheral blood, cord blood, and induced pluripotent stem cells for immunotherapy of malignant tumor cells. Recently, the safety and efficacy of HLA-mismatched allogeneic cord blood-derived CD19 CAR-NK cell therapy for CD19-positive hematological malignancies have been reported. However, the durability of clinical effects has not been clarified. The characteristics of CAR-NK cells with a strong antileukemia/lymphoma effect and better proliferative capacity without severe adverse effects may be promising for overcoming intractable hematological malignancies as an off-the-shelf allogeneic cellular therapy.

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