Inhibition of p38 MAPK activity in B-NHL Raji cells by treatment with engineered CD20-specific T cells

Jiang,Lei; Yu,Kang; Du,Jimei; Ni,Wuhua; Han,Yixiang; Gao,Shenmeng; Li,Haiying; Wu,Jianbo; Zheng,Yihu; Tan,Yingxia

doi:10.3892/ol.2011.308

Inhibition of p38 MAPK activity in B-NHL Raji cells by treatment with engineered CD20-specific T cells

Authors:
- Lei Jiang
- Kang Yu
- Jimei Du
- Wuhua Ni
- Yixiang Han
- Shenmeng Gao
- Haiying Li
- Jianbo Wu
- Yihu Zheng
- Yingxia Tan
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Affiliations: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Department of Hematology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Department of Clinical Laboratory Medicine, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China
Published online on: May 13, 2011 https://doi.org/10.3892/ol.2011.308
Pages: 753-758

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Abstract

Adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell receptors is a promising approach to lymphoma therapy. However, modification of the cellular signaling pathways in target tumor cells by treatment with engineered CD20-specific T cells has yet to be fully elucidated. In this study, the non-Hodgkin's lymphoma Raji cell line was co-cultured with T cells that were genetically modified with anti-CD20scFvFc/CD28/CD3ζ or anti-CD20scFvFc gene. The cytolytic activity of engineered CD20-specific T cells and IL-10 secretion was quantitated by Cytotoxicity and ELISA assays, respectively. The engineered CD20-specific T cells and Raji cells were sorted using flow cytomety for the Western blot analysis. Treatment of Raji cells with T cells genetically modified with anti-CD20scFvFc/CD28/CD3ζ chimera (compared to anti-CD20scFvFc) yielded a higher cytotoxicity against Raji cells in vitro. Additionally, we found that engineered CD20-specific T cells caused a decrease in IL-10 secretion and inhibition of phosphor-STAT3 and Bcl-2 expression in Raji cells, possibly through the down-regulation of p38 MAPK and NF-κB activity. These results indicate that the treatment of Raji cells with engineered CD20-specific T cells inhibited the cellular p38 MAPK signaling pathways, which enhanced its antitumor activities against CD20-positive tumor cells.

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