Treatment With a Fusion Protein of the Extracellular... : Journal of Immunotherapy (original) (raw)

Basic Studies

Treatment With a Fusion Protein of the Extracellular Domains of NKG2D to IL-15 Retards Colon Cancer Growth in Mice

Xia, Yan*; Chen, Bei*; Shao, Xiaoqing*; Xiao, Weiming†; Qian, Li*; Ding, Yanbing†; Ji, Mingchun*; Gong, Weijuan*,†,‡

*Department of Immunology, School of Medicine

†Department of Gastroenterology, the Second Clinical Medical College

‡Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, PR China

Reprints: Weijuan Gong, Department of Immunology, School of Medicine, Yangzhou University, Huaihai Road 11, Yangzhou 225001, Jiangsu Province, PR China (e-mail: [email protected]).

Received June 19, 2013

Accepted February 27, 2014

Abstract

Tumor-targeted cytokines are a new class of pharmaceutical anticancer agents often considered superior to the corresponding unconjugated cytokines for therapeutic purposes. We generated a new fusion protein, dsNKG2D-IL-15, in which double NKG2D extracellular domains were fused to IL-15, in Escherichia coli. This fusion protein promoted the activation, proliferation, and cytotoxicity of NK cells, and bound to NKG2D ligand-positive tumor cells. These tumor cells were also more susceptible to NK-cell attack when decorated with dsNKG2D-IL-15. The administration of mouse dsNKG2D-IL-15 protein in vivo significantly retarded the growth of transplanted colon cancers and prolonged the survival of tumor-bearing mice. Treatment with dsNKG2D-IL-15 increased the frequencies of NK and CD8+ T cells in spleen and tumor tissues. The antitumor effect mediated by dsNKG2D-IL-15 was significantly decreased with in vivo depletion of NK cells or CD8+ T cells. Recombinant dsNKG2D-IL-15 thus inhibited NKG2D ligand-positive tumor growth effectively by activating lymphocytes. This new biological fusion protein could potentially be used to elicit immunity in tumor-targeting treatments.