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In Vivo Developing Immunotherapy of Ex Vivo Expansion of Human Natural Killer Cells from Thalassemia Patients for Leukaemia

Author(s): M. Alkhaled*, A. M. Elazzazy, O. A. Almaghrabia and R. Handgretinger
Department of Biology, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia, 1Department of Paediatric Haematology and Oncology, University Children’s Hospital Tubingen, Tubingen 72076, Germany

Correspondence Address:
M. Alkhaled, Department of Biology, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia, E-mail:

Natural killer cells are specific innate lymphoid cells which have therapeutic ability in adoptive cell transferprimarily based on most cancers immunotherapy that has been installed throughout a variety of earlyphase clinical trials. Natural killer cells to be used in adoptive transfer treatments are received from diverse resources. These cells have attracted widespread interest as adoptive immunotherapy for most cancers because of their preventive antitumor properties. In order to study the efficacy of adoptive natural killer cell immunotherapy in a preclinical manner with clinical translation potential, a reliable ex vivo natural killer cell expansion platform may be required. As a preclinical study, we have designed a humanized mouse model using NOD scid gamma mice, human leukaemia cells and expanded natural killer cells. At the beginning, peripheral blood mononuclear cells from patients with different thalassemia subtypes were co-cultured with irradiated, genetically engineered K562-mb15-41BBL cells in the presence of interleukin-2 for 14 d. Humanized NOD scid gamma mice with human leukaemia were treated with different approaches of natural killer cells, gamma delta cells and clusters of differentiation 20 immunoglobulin G1 antibody. In vivo results show that our strategy of immunotherapy with expanded natural killer cells has extended survival of mice. Flow cytometry results from the peripheral blood mononuclear cells of the treated mice showed that the expanded natural killer cells have potential ability to effectively kill the leukaemia cells. Based on these findings, adoptive transfer of expanded and activated natural killer cells ex vivo is gaining similar clinical evaluation as a potential new therapeutic alternative for patients with tumors and other immunological diseases.

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