alloreactive natural killer cells

Alloreactive natural killer cells (NK cells) are a type of immunotherapy that harnesses the body's natural immune system to target and eliminate cancer cells, particularly in acute myeloid leukemia (AML). These specialized cells are derived from donors whose killer immunoglobulin-like receptors (KIRs) are mismatched with the recipient's human leukocyte antigen (HLA) ligands, creating a potent graft-versus-leukemia effect without causing graft-versus-host disease. ## Description Alloreactive natural killer cells are a form of adoptive cell therapy used primarily in the treatment of acute myeloid leukemia (AML). These cells are derived from donors whose killer immunoglobulin-like receptors (KIRs) are mismatched with the recipient's human leukocyte antigen (HLA) ligands. This mismatch allows the NK cells to recognize and attack cancer cells while sparing healthy tissues. The therapeutic approach involves collecting NK cells from a haploidentical donor (typically a family member who is partially HLA-matched), purifying and sometimes expanding them ex vivo, and then infusing them into patients following lymphodepleting chemotherapy. The conditioning regimen, often consisting of fludarabine and cyclophosphamide, helps create space for the infused NK cells and reduces host immune rejection. Research has shown that the dose of alloreactive NK cells is critical for treatment response, with studies identifying a functional dose of approximately 2 × 10^5/kg alloreactive NK cells as predictive of response in AML patients. These cells can persist in the recipient's body for up to 28 days post-infusion, especially when exogenous interleukin (IL)-2 is administered to support their survival and proliferation. Clinical trials have demonstrated the safety and feasibility of alloreactive NK cell therapy in both adult and pediatric patients with AML, particularly in relapsed/refractory cases or as post-remission therapy to prevent relapse. The treatment is generally well-tolerated with minimal side effects, and importantly, does not cause graft-versus-host disease, which is a significant advantage over traditional allogeneic stem cell transplantation. ## Development Status Alloreactive natural killer cells are currently in clinical development for several conditions: - Acute Myeloid Leukemia (AML): PHASE2 - Hematologic Malignancies: IN DEVELOPMENT

Other names

haploidentical NK cellsKIR-L mismatched NK cellsalloreactive NK cellsdonor-derived alloreactive NK cells