Allogeneic cell therapy for the regulation of GVHD/GVL

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Inhibitory natural killer cell receptor (NKR)-expressing cells may induce a graft-versus-leukemia/tumor (GVL/T) effect against leukemic cells and tumor cells that have mismatched or decreased expression of HLA class I molecules and may not cause graft-versus-host disease (GVHD) against host cells that have normal expression of HLA class I molecules. In our study, we were able to expand inhibitory NKR (CD94/NKG2A)-expressing CD8^+ T cells from G-CSF-mobilized peripheral blood mononuclear cells (G-PBMCs) by more than 500 fold using stimulation by an anti-CD3 monoclonal antibody with IL-15. These expanded and purified CD94-expressing cells attacked various malignant cell lines, including solid cancer cell lines, as well as the patients' leukemic cells but not autologous and allogeneic PHA blasts in vitro. Also, these CD94-expressing cells prevented the growth of K562 leukemic cells and also CW2 colon cancer cells in NOD/SCID mice in vivo. On the other hand, the CD94-expressing cells have low responsiveness to alloantigen in MLC and also have high TGF-β1-but low IL-2-producing capacity. Therefore, CD94-expressing cells with cytolytic activity against the recipient's leukemic and tumor cells without enhancement of alloresponse might be able to be expanded from donor G-PBMCs.