University Children's Hospital of Frankfurt/Main and Department of Pediatric Hematology, Oncology and Hemostaseology, Goethe-University Frankfurt/Main, Frankfurt/Main, Germany.
Cytotherapy. 2012 Jan;14(1):91-103. doi: 10.3109/14653249.2011.613931. Epub 2011 Oct 6.
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.
细胞因子诱导的杀伤（CIK）细胞可作为同种异体造血干细胞移植（HSCT）后复发的急性白血病患者过继供体淋巴细胞输注（DLI）的替代方法。我们研究了白细胞介素（IL）-15 增强 CIK 细胞对急性髓系和淋巴母细胞性白血病/淋巴瘤细胞的细胞毒性的可行性。
使用白细胞介素（IL）-2（CIK（IL-2））或白细胞介素（IL）-15（CIK（IL-15））激活 CIK 细胞，并通过荧光激活细胞分选（FACS）进行表型分析。通过 Eu 释放测定测量细胞毒性潜力。
CIK（IL-2）细胞对 T 淋巴细胞白血病细胞系 H9、T 细胞急性淋巴细胞白血病（T-ALL）细胞系 MOLT-4 和亚型 M4 急性髓系白血病（AML）细胞系 THP-1 具有强大的细胞毒性，但对前体 B（pB）-细胞 ALL 细胞系 Tanoue 的细胞毒性较低。IL-15 刺激导致 CIK 细胞对急性淋巴细胞白血病/淋巴瘤细胞系以及原发性急性髓系和明确的淋巴母细胞白血病细胞的细胞毒性显著增强。然而，CIK（IL-15）细胞的同种异体反应潜能仍然较低。对 CIK（IL-15）细胞的进一步分析表明，NKG2D 受体显然参与了靶细胞的识别，而杀伤细胞免疫球蛋白样受体（KIR）-HLA 错配对 CIK（IL-15）细胞介导的细胞毒性的贡献较小。在这种情况下，CD3（+）CD8（+）CD25（+）CD56（-）CIK（IL-15）细胞亚群在 AML 细胞的溶解中更有效，而 CD56（+）CIK（IL-15）细胞对 ALL 细胞具有最高的细胞毒性。
这项研究首次提供了证据，表明 CIK（IL-15）细胞可能为同种异体 HSCT 后复发或难治性白血病患者提供一种治疗选择。
