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Mouse tumor vasculature expresses NKG2D ligands and can be targeted by chimeric NKG2D-modified T cells.


ABSTRACT: Tumor angiogenesis plays an important role in the development of solid tumors, and targeting the tumor vasculature has emerged as a strategy to prevent growth and progression of solid tumors. In this study, we show that murine tumor vasculature expresses Rae1, a ligand for a stimulatory NK receptor NKG2D. By genetic modification of T cells with an NKG2D-based chimeric Ag receptor, referred to as chNKG2D in which the NKG2D receptor is fused to the signaling domain of CD3?-chain, T cells were capable of targeting tumor vasculature leading to reduced tumor angiogenesis and tumor growth. This occurred even in tumors where the tumor cells themselves did not express NKG2D ligands. H5V, an endothelial cell line, expresses Rae1 and was lysed by chNKG2D-bearing T cells in a perforin-dependent manner. In vitro capillary tube formation was inhibited by chNKG2D T cells through IFN-? and cell-cell contact mechanisms. The in vivo antiangiogenesis effects mediated by chNKG2D-bearing T cells at the tumor site were dependent on IFN-? and perforin. These results provide a novel mechanism for NKG2D-based targeting of solid tumors.

SUBMITTER: Zhang T 

PROVIDER: S-EPMC3665362 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Mouse tumor vasculature expresses NKG2D ligands and can be targeted by chimeric NKG2D-modified T cells.

Zhang Tong T   Sentman Charles L CL  

Journal of immunology (Baltimore, Md. : 1950) 20130125 5


Tumor angiogenesis plays an important role in the development of solid tumors, and targeting the tumor vasculature has emerged as a strategy to prevent growth and progression of solid tumors. In this study, we show that murine tumor vasculature expresses Rae1, a ligand for a stimulatory NK receptor NKG2D. By genetic modification of T cells with an NKG2D-based chimeric Ag receptor, referred to as chNKG2D in which the NKG2D receptor is fused to the signaling domain of CD3ζ-chain, T cells were capa  ...[more]

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