The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells.

Rettinger, Eva, KuçI, Selim, Naumann, Ivonne, Becker, Petra, Kreyenberg, Hermann, Anzaghe, Martina, Willasch, Andre, Koehl, Ulrike, Bug, Gesine, Ruthardt, Martin ORCID: https://orcid.org/0000-0003-1021-3811, Klingebiel, Thomas, Fulda, Simone and Bader, Peter 2012. The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells. Cytotherapy 14 (1) , pp. 91-103. 10.3109/14653249.2011.613931

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Abstract

Cytokine-induced killer (CIK) cells may serve as an alternative approach to adoptive donor lymphocyte infusions (DLI) for patients with acute leukemia relapsing after haplo-identical hematopoietic stem cell transplantation (HSCT). We investigated the feasibility of enhancing CIK cell-mediated cytotoxicity by interleukin (IL)-15 against acute myeloid and lymphoblastic leukemia/lymphoma cells.CIK cells were activated using IL-2 (CIK(IL-2)) or IL-15 (CIK(IL-15)) and phenotypically analyzed by fluorescence-activated cell sorting (FACS). Cytotoxic potential was measured by europium release assay.CIK(IL-2) cells showed potent cytotoxicity against the T-lymphoma cell line H9, T-cell acute lymphoblastic leukemia (T-ALL) cell line MOLT-4 and subtype M4 acute myeloid leukemia (AML) cell line THP-1, but low cytotoxicity against the precursor B (pB)-cell ALL cell line Tanoue. IL-15 stimulation resulted in a significant enhancement of CIK cell-mediated cytotoxicity against acute lymphoblastic leukemia/lymphoma cell lines as well as against primary acute myeloid and defined lymphoblastic leukemia cells. However, the alloreactive potential of CIK(IL-15) cells remained low. Further analysis of CIK(IL-15) cells demonstrated that the NKG2D receptor is apparently involved in the recognition of target cells whereas killer-cell immunoglobulin-like receptor (KIR)-HLA mismatches contributed to a lesser extent to the CIK(IL-15) cell-mediated cytotoxicity. In this context, CD3 (+) CD8 (+) CD25 (+) CD56(-) CIK(IL-15) cell subpopulations were more effective in the lysis of AML cells, in contrast with CD56 (+) CIK(IL-15) cells, which showed the highest cytotoxic potential against ALL cells.This study provides the first evidence that CIK(IL-15) cells may offer a therapeutic option for patients with refractory or relapsed leukemia following haplo-identical HSCT.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	1465-3249
Date of Acceptance:	8 August 2011
Last Modified:	21 Feb 2024 16:15
URI:	https://orca.cardiff.ac.uk/id/eprint/166087

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