A clinical study of cytokine-induced killer cells for the treatment of refractory lymphoma

Guo,Zhi; Liu,Hao; He,Xue-Peng; Tan,Xiao-Hua; Zhou,Yan; Chen,Xia; Shi,Yu-Jie; Liu,Xiao-Dong; Chen,Hui-Ren

doi:10.3892/ol.2011.269

May-June 2011 Volume 2 Issue 3

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May-June 2011 Volume 2 Issue 3

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Article

A clinical study of cytokine-induced killer cells for the treatment of refractory lymphoma

Authors:
- Zhi Guo
- Hao Liu
- Xue-Peng He
- Xiao-Hua Tan
- Yan Zhou
- Xia Chen
- Yu-Jie Shi
- Xiao-Dong Liu
- Hui-Ren Chen
View Affiliations / Copyright

Affiliations: Department of Hematology, Beijing Military General Hospital, the Affiliated Hospital of Anhui Medical University, Beijing, P.R. China
Pages: 531-536
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Published online on: March 15, 2011

https://doi.org/10.3892/ol.2011.269
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Abstract

Cytokine-induced killer (CIK) cell therapy, an adoptive T-cell immunotherapy, has been reported to be a safe and effective mode of treatment for patients with metastatic diseases, lymphoma and acute leukaemia. To investigate the clinical efficacy of cytokine-induced killer cells for the treatment of refractory lymphoma, the present clinical study was conducted. A total of 8 male patients with a mean age of 41 years (range 22-65) who were pathologically diagnosed with malignant lymphoma (Hodgkin's disease, 2 and non-Hodgkin's lymphoma, 6) were enrolled. CIK cells were expanded by priming with IFN-γ, monoclonal antibody (mAb) to CD3 and IL-1α, followed by the addition of IL-2 the following day using peripheral blood mononuclear cells (PBMCs) of the 8 male patients. The CIK cells were then transfused back to the patients as treatment. On day 13, the CIK cell count reached 7-18x1019 (mean, 12.7x109), a 44- to 140-fold increase (mean, 98-fold). The average percentage of cells expressing CD3+, CD4+, CD8+ and CD3+CD56+ were also increased from 50.9±3.5, 29.9±1.7, 41.3±3.2, 1.6±0.2% to 90.2±1.6, 40.6±5.5, 52.8±4.9 and 33.1±4.0%, respectively. Patients showed measurable radiographic tumor reduction, increased T-cell subset levels, and relief of symptoms after treatment. No severe toxicity or side effects were reported. CIK cells developed by this culture method have a high in vitro proliferation rate and tumor-killing capacity. In conclusion, CIK cell treatment of patients with malignant lymphoma achieves effective clinical responses, causing few side effects.

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1	Schmidt-Wolf IG, Negrin RS, Kiem HP, et al: Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. Exp Med. 174:139–149. 1999. View Article : Google Scholar : PubMed/NCBI
2	Linn YC and Hui KM: Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Leuk Lymphoma. 44:1457–1462. 2003. View Article : Google Scholar : PubMed/NCBI
3	Leemhuis T, Wells S, Scheffold C, et al: A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 11:181–187. 2005. View Article : Google Scholar : PubMed/NCBI
4	Chan JK, Hamilton CA, Cheung MK, et al: Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study. Clin Cancer Res. 12:1859–1867. 2006. View Article : Google Scholar : PubMed/NCBI
5	Shi M, Zhang B, Tang ZR, et al: Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma. Clin Trial. 10:1146–1151. 2004.PubMed/NCBI
6	Kuci S, Rettinger E, Voss B, et al: Efficient lysis of rhabdomyosarcoma cells by cytokine-induced killer cells: implications for adoptive immunotherapy after allogeneic stem cell transplantation. Haematologica. 95:1579–1586. 2010. View Article : Google Scholar : PubMed/NCBI
7	Sangiolo D, Mesiano G, Carnevale SF, et al: Cytokine induced killer cells as adoptive immunotherapy strategy to augment graft versus tumor after hematopoietic cell transplantation. Expert Opin Biol Ther. 9:831–840. 2009. View Article : Google Scholar
8	Nishimura R, Baker J, Beilhack A, et al: In vivo trafficking and survival of cytokine-induced killer cells resulting in minimal GVHD with retention of anti-tumor activity. Blood. 112:2563–2574. 2008. View Article : Google Scholar
9	Sangiolo D, Martinuzzi E, Todorovic M, et al: Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers. Inter Immunol. 20:841–848. 2008. View Article : Google Scholar
10	Alvarnas JC, Linn YC, Hope EG, et al: Expansion of cytotoxic CD3⁺CD56⁺ cells from peripheral blood progenitor cells of patients undergoing autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 7:216–222. 2001.
11	Kornacker M, Moldenhauer G, Herbst M, et al: Cytokine-induced killer cells against autologous CLL: direct cytotoxic effects and induction of immune accessory molecules by interferon-gamma. Int J Cancer. 119:1377–1382. 2006. View Article : Google Scholar
12	Mehta BA, Schmidt-Wolf IG, Weissman IL, et al: Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3⁺CD56⁺ killer cells. Blood. 86:3493–3499. 1995.PubMed/NCBI
13	Verneris MR, Karami M, Baker J, et al: Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8⁺ T cells. Blood. 103:3065–3072. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A clinical study of cytokine-induced killer cells for the treatment of refractory lymphoma

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