title: Inhibition of p38 MAPK activity in B-NHL Raji cells by treatment with engineered CD20-specific T cells.
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.
authors: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors: Lei
authors: L
authors: Jiang
authors: Kang
authors: K
authors: Yu
authors: Jimei
authors: J
authors: DU
authors: Wuhua
authors: W
authors: Ni
authors: Yixiang
authors: Y
authors: Han
authors: Shenmeng
authors: S
authors: Gao
authors: Haiying
authors: H
authors: Li
authors: Jianbo
authors: J
authors: Wu
authors: Yihu
authors: Y
authors: Zheng
authors: Yingxia
authors: Y
authors: Tan