LIGHT protein suppresses tumor growth by augmentation of immune response.
The tumor necrosis factor (TNF) superfamily member LIGHT has potent anti-tumor activities through activation of the immune response, and it is a promising candidate for use in cancer immunotherapy. However, there are no reports of the anti-tumor effects of LIGHT protein in vivo because of the lack of easy, efficient methods of manufacturing this protein. Here, we developed a method of manufacturing recombinant LIGHT protein using Escherichia coli through refolding of inclusion bodies; we then evaluated the anti-tumor activity of the protein. LIGHT protein expressed in E. coli showed the same biological activities and binding affinities to its receptors as did LIGHT expressed in mammalian cells. In addition, intratumoral injection of LIGHT significantly suppressed tumor growth, with augmentation of antigen-specific IFN-gamma-producing cells in the regional lymph nodes and spleen. These results indicate that LIGHT protein efficiently evokes the systemic tumor-specific immune response, and thus induces tumor suppression.
Morishige
Tomohiro
T
Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yoshioka
Yasuo
Y
Inakura
Hiroshi
H
Tanabe
Aya
A
Watanabe
Hikaru
H
Yao
Xinglei
X
Tsunoda
Shin-Ichi
S
Tsutsumi
Yasuo
Y
Mukai
Yohei
Y
Okada
Naoki
N
Nakagawa
Shinsaku
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D048708:Cell Growth Processes; D003001:Cloning, Molecular; D004926:Escherichia coli; D019073:HT29 Cells; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics
D000951:Antigens, Neoplasm; D011994:Recombinant Proteins; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D007371:Interferon-gamma