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Allogeneic double negative T cells (DNTs) are an off-the-shelf adoptive cellular immunotherapy consisting of mature CD3+CD4-CD8- T lymphocytes derived from healthy donors. These cells represent a rare subset of peripheral blood leukocytes (1-5%) and are characterized by their ability to kill various cancer cells, particularly in hematological malignancies, without requiring HLA matching or inducing graft-versus-host disease (GvHD). The anti-tumor mechanism of DNTs is primarily mediated through the NKG2D and DNAM-1 signaling pathways, which recognize stress-induced ligands on the surface of malignant cells. DNTs also produce high levels of interferon-gamma (IFN-gamma) upon activation, further enhancing their cytotoxic potential. This therapy is being developed for chemotherapy-resistant acute myeloid leukemia (AML) and B-cell malignancies, with some versions engineered to express chimeric antigen receptors (CARs), such as the anti-CD19 product RJMty19.
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