The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells.
Cytotherapy
; 14(1): 91-103, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21973023
ABSTRACT
BACKGROUND AIMS:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Adyuvantes Inmunológicos
/
Inmunoterapia Adoptiva
/
Linfocitos Infiltrantes de Tumor
/
Interleucina-15
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Subfamilia K de Receptores Similares a Lectina de Células NK
Límite:
Humans
Idioma:
En
Revista:
Cytotherapy
Asunto de la revista:
TERAPEUTICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Alemania