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Volume 18, Issue 2 (June-2026 2026)
Iranian Journal of Blood and Cancer 2026, 18(2): 88-95 |
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Minaei N, Tayebi B, Torabi S, Ebrahimi M, Piryaei A, Vosough M. Optimization of IL-15–Enriched Cytokine-Induced Killer Cells Expansion: Phenotypic and Functional Characterization. Iranian Journal of Blood and Cancer 2026; 18 (2) :88-95
URL: http://ijbc.ir/article-1-1929-en.html
URL: http://ijbc.ir/article-1-1929-en.html
Neda Minaei1 
, Behnoosh Tayebi2 , Shukoofeh Torabi3 , Marzieh Ebrahimi4 , Abbas Piryaei5 , Massoud Vosough *6
, Behnoosh Tayebi2 , Shukoofeh Torabi3 , Marzieh Ebrahimi4 , Abbas Piryaei5 , Massoud Vosough *6
1- Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies, Royan Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran. & Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
2- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
3- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. & Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
4- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
5- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. & Urogenital Stem Cell Research Center, Research Institute for Urology and Nephrology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6- Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies, Royan Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran & Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. & Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital-Huddinge, Huddinge, Sweden. ,masvos@yahoo.com
2- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
3- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. & Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
4- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
5- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. & Urogenital Stem Cell Research Center, Research Institute for Urology and Nephrology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6- Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies, Royan Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran & Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. & Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital-Huddinge, Huddinge, Sweden. ,
Abstract: (4 Views)
Background: In adoptive cell therapy, cytokine-induced killer (CIK) cells have been used as a promising modality due to their potent antitumor activity and MHC-independent function. IL-15 has been proposed as a promising alternative to IL-2 because it enhances survival, maintains a memory-like phenotype, and improves cytotoxic function; however, its utility in optimizing CIK cells for the treatment of hepatocellular carcinoma (HCC) remains to be investigated.
Methods: CIK cells were generated from human peripheral blood mononuclear cells (hPBMCs) using a 12-day step-wise expansion protocol including treatment with IFN-γ, anti-CD3 antibody, IL-2, and IL-15 in culture medium containing human platelet lysate. The phenotypic characteristics of the cells were examined by flow cytometry, and the expression of CD3⁺, CD8⁺, and CD56⁺ was assessed. The cytotoxic activity of CIK cells against HepG2 cells was evaluated by flow cytometry using a CFSE/PI assay at different effector-to-target ratios (E: T), and ELISA measured the secretion of IFN-γ and TNF-α.
Results: The expanded CIK cells exhibited a characteristic CD3⁺CD8⁺ and CD3⁺CD56⁺ phenotype. These cells demonstrated significant cytotoxic activity against HepG2 cells across different E: T ratio and showed enhanced production of IFN-γ and TNF-α, indicating robust antitumor activity.
Conclusion: The short-term IL-15-enriched expansion protocol generated stable CIK cells with an NK-like phenotype and significant cytotoxic activity against HCC cells. Increased secretion of inflammatory cytokines also indicated effective antitumor activation of these cells. These findings support further development and preclinical evaluation of IL-15-CIK-based cell therapy for the treatment of HCC.
Methods: CIK cells were generated from human peripheral blood mononuclear cells (hPBMCs) using a 12-day step-wise expansion protocol including treatment with IFN-γ, anti-CD3 antibody, IL-2, and IL-15 in culture medium containing human platelet lysate. The phenotypic characteristics of the cells were examined by flow cytometry, and the expression of CD3⁺, CD8⁺, and CD56⁺ was assessed. The cytotoxic activity of CIK cells against HepG2 cells was evaluated by flow cytometry using a CFSE/PI assay at different effector-to-target ratios (E: T), and ELISA measured the secretion of IFN-γ and TNF-α.
Results: The expanded CIK cells exhibited a characteristic CD3⁺CD8⁺ and CD3⁺CD56⁺ phenotype. These cells demonstrated significant cytotoxic activity against HepG2 cells across different E: T ratio and showed enhanced production of IFN-γ and TNF-α, indicating robust antitumor activity.
Conclusion: The short-term IL-15-enriched expansion protocol generated stable CIK cells with an NK-like phenotype and significant cytotoxic activity against HCC cells. Increased secretion of inflammatory cytokines also indicated effective antitumor activation of these cells. These findings support further development and preclinical evaluation of IL-15-CIK-based cell therapy for the treatment of HCC.
Keywords: Immunotherapy, Adoptive cell therapy, Cytokine-induced killer cells, Hepatocellular carcinoma
: Original Article |
Subject:
Immunology
Received: 2026/05/13 | Accepted: 2026/06/27 | Published: 2026/06/9
Received: 2026/05/13 | Accepted: 2026/06/27 | Published: 2026/06/9
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