Adoptive immunotherapy with cytokine-induced killer cells generated with a new good manufacturing practice-grade protocol

Rutella, Sergio; Iudicone, Paola; Bonanno, Giuseppina; Fioravanti, Daniela; Procoli, Annabella; Lavorino, Claudio; Foddai, Maria Laura; Lorusso, Domenica; Martinelli, Elisa; Vacca, Michele; Ipsevich, Francesco; Nuti, Marianna; Scambia, Giovanni; Pierelli, Luca

doi:10.3109/14653249.2012.681038

Cited by 24 publications

(13 citation statements)

References 24 publications

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“…A sub-population of the T-lymphocytes, differentiated in vitro by addition of specific cytokines to the media culture is the cytokine-induced killer (CIK) cells. The CIK cells are major histocompatibility complex (MHC)-unrestricted with the characteristic CD3 + CD56 + phenotype and they have been shown, in vitro and in medical practice, to be efficient killers of tumor cells (9,(17)(18)(19). These CIK cells with the ability to attack tumor cells are expressed on the cell surface of CD3/CD56.…”

Section: Cytokine-induced Killer Cells Co-cultured With Complete Tumomentioning

confidence: 99%

“…Adoptive immunotherapy uses the natural ability of the immune system to recognize and eliminate continuously arising transformed cells. This approach can be efficiently employed for the eradication of residual cancer cells and prevention or delay of tumor relapse (9). An example is the case of solid tumors, where antigen-specific immunotherapy has emerged as a promising approach (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells

et al. 2013

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Abstract. Retinoblastoma (RB) is a challenging disease that affects mostly young children. Chemical therapy has been shown to have limitations during clinical practice, principally because of the ability of RB to become resistant to the treatment. Nevertheless, chemotherapy is still the main treatment for RB, and immunotherapy has become a promising treatment for most solid tumors with fewer side effects than traditional therapies. In this study, we explored the antitumor effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) pulsed with complete tumor antigens (DC-Ag). Cytotoxicity and specificity were evaluated on an RB cell line (RB-Y79), on a human normal retina cell line (hTERT-RPE1) and a carboplatin-resistant RB cell line. Our results showed that CIK differentiation and cytotoxicity were enhanced by co-culturing CIKs with DC-Ag. Moreover, the co-culture improved the CIK proliferation rate by increasing IL-6 and decreasing IL-10 levels in the culture medium. Furthermore, the use of DC-Ag-CIK cells had little effect on normal retinal cells but high cytotoxicity on RB cells even on carboplatinresistant retinoblastoma cells. This is the first study showing that DC cells pulsed with the complete tumor antigen improve proliferation, differentiation and cytotoxic activity of CIKs specific not only for RB but also for the chemotherapy-resistant form of the malady. Thus highly efficient immunotherapy based on DC-Ag-CIK cells may be a potential effective and safe mean of treating RB especially to patients where traditional chemical therapy has failed.

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Section: Cytokine-induced Killer Cells Co-cultured With Complete Tumomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells

et al. 2013

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“…Rettinger et al (7) and Meng et al (8) demonstrated that IL-15 and IL-21, respectively were able to promote the proliferative, and cytotoxic activity of cytokine-induced killer cells (CIKs). Rutella et al (9) noted that thymoglobulin efficiently expanded the CIK population, and that the CIKs generated by thymoglobulin were feasible and safe for solid tumor treatment. Tan et al (10) verified that K-ras dendritic cells were able to enhance CIK proliferation and increase the killing effect on pancreatic cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Identification of a protein associated with the activity of cytokine‑induced killer cells

et al. 2017

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Abstract. Cytokine-induced killer cells (CIKs) adoptive immunotherapy for efficient antitumor ability is used clinically, but details regarding the proteins associated with CIK activity remain unclear. In the current study, the cytotoxicity of CIKs on hepatoma was identified to be significantly downregulated by 1.61-fold following gentamincin treatment. Further research revealed that a differentially expressed protein (P43) was significantly downregulated by 1.22-fold using one-dimensional gel electrophoresis analysis. Of these, the P43 was identified as human haptoglobin using liquid chromatography-mass spectrometry. Western blotting demonstrated that the haptoglobin specifically reacted with rabbit anti-human-haptoglobin. Furthermore, western blotting results verified that the haptoglobin was significantly downregulated by 1.17-fold compared with the control group. In addition, the expression of haptoglobin mRNA was significantly downregulated by 1.73-fold following gentamincin treatment. Taken together, the results of the present study demonstrated that the expression of haptoglobin protein was associated with the activity of CIKs, and the results will be beneficial to the further investigation of CIK activity-enhancement mechanism.

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“…CIK cells form CD3+CD56+ and CD3+CD8+ based heterogenetic cell colonies; these cells are immune effectors with powerful killing activity and have been considered to be good prospects for inducing adoptive immunotherapy [5,6]. Several clinical trials have investigated the use of CIK cells for the treatment of malignant solid tumors and have confirmed that these cells have good curative effects [7–11]. …”

Section: Introductionmentioning

confidence: 99%

Curative Effects of Dendritic Cells Combined with Cytokine-Induced Killer Cells in Patients with Malignant Pericardial Effusion

et al. 2016

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BackgroundTo determine the effects of dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with malignant pericardial effusion.Material/MethodsAll patients underwent pericardial puncture and indwelling catheter insertion. After pericardial drainage, the 16 patients in the treatment group received an infusion of 20 mL DCs and CIK cells (>1.0×1010 cells) and 500,000 U interleukin (IL)-2 for 3 successive days. The 15 control-group patients received 30 mg/m2 cisplatin and 500,000 U IL-2 for 3 successive days. The treatment effects were assessed using imaging data.ResultsThe total efficiency and complete remission rates were higher in the treatment group than in the control group at 4 weeks (total efficiency: 87.50% vs. 73.33%; complete remission: 62.50% vs. 46.67%) and 3 months after the treatment (total efficiency: 81.25% vs. 66.67%; complete remission: 50.00% vs. 40.00%; P<0.05 for all). In both groups, the Karnofsky scores for quality of life improved after treatment. However, the curative effects were better in the treatment group than in the control group (P<0.05). The following adverse reactions occurred: fever, 6 treatment-group patients and 3 control-group patients; chest pain, 2 treatment-group patients and 7 control-group patients; gastrointestinal reactions, 1 treatment-group patient and 6 control-group patients; and bone marrow suppression, 1 treatment-group patient and 5 control-group patients. The between-group differences in adverse reactions were significant (P<0.05).ConclusionsThe combination of DCs and CIK cells effectively treated malignant pericardial effusion, produced few side effects, and improved the patients’ quality of life.

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Adoptive immunotherapy with cytokine-induced killer cells generated with a new good manufacturing practice-grade protocol

Cited by 24 publications

References 24 publications

Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells

Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells

Identification of a protein associated with the activity of cytokine‑induced killer cells

Curative Effects of Dendritic Cells Combined with Cytokine-Induced Killer Cells in Patients with Malignant Pericardial Effusion

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