Potential therapeutic strategy for gastric cancer peritoneal metastasis by NKG2D ligands-specific T cells.

Abstract

PURPOSE:

Despite advancements in its treatment, gastric cancer continues to be one of the leading causes of cancer deaths worldwide. Adoptive transfer of chimeric antigen receptor-modified T cells is a promising antitumor therapy for many cancers. The purpose of this study was to construct a chimeric receptor linking the extracellular domain of NKG2D to the CD28 and CD3zeta chain intracellular domains to target gastric cancers that expressed NKG2D ligands.

METHODS:

Expression of NKG2D ligands including MICA, MICB, and ULBP1-3 in a gastric cancer cell line and primary gastric cancer cells from ascites samples were analyzed using flow cytometry. Co-culture experiments were performed by incubating chNKG2D T cells with gastric cancer cell lines and with primary human gastric cancer cells isolated from ascites and by measuring cytokine and chemokine release and cytotoxicity.

RESULTS:

Gastric cancer cell lines and ascites-derived primary human gastric cancer cells expressed high levels of MICA, MICB, and ULBP2. ChNKG2D T cells secreted proinflammatory cytokines and chemokines when cultured with these cancer cells. In addition, chNKG2D T cells lysed gastric cancer cell lines and the ascites-derived primary human gastric cancer cells.

CONCLUSION:

These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for gastric cancer with peritoneal metastasis.

• Authors: Xianqiang Liu, Meili Sun, Shui Yu, Kai Liu, Xirui Li, Huan Shi
• Journal: OncoTargets and therapy (Onco Targets Ther) Vol. 8 Pg. 3095-104 ( 2015) ISSN: 1178-6930 [Print] New Zealand
• PMID: 26543378 (Publication Type: Journal Article)