Augmented CD3+CD8+ and CD3+CD56− cells in cytokine-induced killer cells cultured with engineered cells for costimulatory enhancement from heavily pretreated patients with solid tumor
| Autor: | Wei Zhao, Zhenxian Zhou, Dandan Yin, Yongxiang Yi, Wei Ye, Lili Wang, Jing Fan |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Cancer Research CD3 Complex CD8 Antigens CD3 medicine.medical_treatment Immunology Biology Lymphocyte Activation Immunotherapy Adoptive 03 medical and health sciences Cytokine-Induced Killer Cells 0302 clinical medicine Co-stimulation Interferon Neoplasms medicine Humans Immunology and Allergy Cytotoxic T cell Cell Engineering Cells Cultured Genetics (clinical) Aged Salvage Therapy Transplantation Cytokine-induced killer cell Cell Biology Middle Aged CD56 Antigen Cytokine Oncology 030220 oncology & carcinogenesis biology.protein Female Tumor necrosis factor alpha K562 Cells CD8 030215 immunology medicine.drug |
| Zdroj: | Cytotherapy. 18:581-589 |
| ISSN: | 1465-3249 |
| Popis: | Background aims Cytokine-induced killer cells (CIKs) were shown to be a promising tool in the quest for new therapeutic approaches in the setting of metastatic solid tumors refractory to standard treatments. However, there is a practical clinical problem of different expansion rates and cell function as individual variability exists. Stimulatory molecular 4-1BB could promote division and survival of T cells and enhance effector activity including cytokine production. This study aimed to invest the contribution of co-stimulation signal to CIKs production for exploring new strategies, which increase the expansion and reliability of CIKs generation to improve access to CIKs therapy. Methods We studied the larger-scale expansion of CIKs cultured with engineered cells for costimulatory enhancement (ECCE) consisting of K562 cells that expressed 4-1BBL in heavily pretreated patients with solid tumor. The proliferation and cytotoxic capacity of CIKs were evaluated. Phenotypes of CIKs were analyzed using flow cytometry. Cytokine levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected using enzyme-linked immunosorbent assay (ELISA). Results The proliferation and cytotoxic activity of CIKs were significantly up-regulated by ECCE. The percentages of CD3 + CD8 + and CD3 + CD56 − CIKs were significantly increased while the percentage of CD3 + CD56 + CIKs was decreased. In addition, the secretion of IFN-γ and TNF-α by CIKs could also be enhanced significantly when ECCE were added into the culture system. Conclusions This study suggests that ECCE may improve the efficacy of CIKs therapy and make CIKs therapy possible for the patients whose CIKs would be hard to be cultured using conventional methods. |
| Databáze: | OpenAIRE |
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