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

Wang,Ya-Feng; Kunda,Patricia   E.; Lin,Jian-Wei; Wang,Han; Chen,Xue-Mei; Liu,Qiu-Ling; Liu,Tao

doi:10.3892/or.2013.2315

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

Authors:
- Ya-Feng Wang
- Patricia E. Kunda
- Jian-Wei Lin
- Han Wang
- Xue-Mei Chen
- Qiu-Ling Liu
- Tao Liu
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Affiliations: Graduate Division, Xinxiang Medical University, Xinxiang, He'nan 453003, P.R. China, Poten Biomedical Institute for Cancer Immunotherapy, Shenzhen, Guangdong 518000, P.R. China, Department of Pediatrics, The General Hospital of the Chinese People's Armed Police Forces, Beijing 100039, P.R. China
Published online on: February 28, 2013 https://doi.org/10.3892/or.2013.2315
Pages: 1841-1850

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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 carboplatin-resistant 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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