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Schlegel, Patrick; Lang, Anne-Marie; Matela, Marie; Horrer, Annika; Schilling, Anne; Joechner, Alexander; Wiedenmann, Max; Seitz, Christian; Döring, Michaela; Feuchtinger, Tobias; Heubach, Florian; Rabsteyn, Armin; Handgretinger, Rupert; Lang, Peter (2019): Ex vivo expansion of autologous, donor-derived NK-, gamma delta T-, and cytokine induced killer (CIK) cells post haploidentical hematopoietic stem cell transplantation results in increased antitumor activity. In: Bone Marrow Transplantation, Vol. 54: pp. 727-732
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Abstract

Posttransplant treatment strategies are narrowed by the vulnerability of bone marrow. Building on immune cells with antitumor activity is a growing field in cancer therapy. Thus, transfer of expanded and preactivated immune cells is a promising intensification of treatment in high-risk tumor patients. We tested ex vivo expanded NK-, gamma delta T-, and CIK cells that were generated by coincubation with irradiated K562-mb15-41BBL and Il2 and compared the expansion conditions of PBMCs versus CD3-depleted PBMCs as well as static versus semi-automated expansion. The median fold expansion was significantly higher using PBMCs and static expansion conditions. Expanded cells were preactivated with a CD56(bright)CD69(high) immunophenotype exerting excellent direct cellular cytotoxicity as well as ADCC in various tumor entities. We established a large-scale clinical-grade ex vivo expansion and activation protocol of NK-, gamma delta T-, and CIK cells from donor-derived PBMCs of patients after haploidentical HSCT. In a patient with AML, NK/gamma delta T/CIK cell transfer was associated with MRD response. A significant increase of direct antitumor activity and ADCC post cell transfer was documented. The results that we report here provide the rationale for clinical testing of expanded, preactivated NK/gamma delta T/CIK cells for cancer therapy.