Evidence indicating the following fact has been found: specific saccharide chains and proteins that bind to the same play a lot of various roles and functions in physiological phenomena, events associated with development/growth, and a variety of diseases in mammal's living bodies. It has been found that there are animal lectins, in living bodies, which specifically recognize saccharide chains with β-galactoside structure. Until now at least 14 types of genes have been identified for galectins which belong to the group of such lectins. Although the galectin family is classified, based on their structure, into three subgroups, i.e., prototype, chimera, and tandem repeat groups, the in vivo functions have scarcely been disclosed. Particularly, a study on tandem repeat type galectins retaining two carbohydrate recognition domains has only a short history. Since in vivo saccharide chains (receptors) to be targeted are still not revealed, the functions are not yet clarified. From details including how galectins were found when a search was made for proteins which recognize complicated sugar chains on the surface of cells, it is forecasted that they have functions such as involvement in cell adhesion, cell-to-cell communication, cell activation, etc. Therefore, galectins attract attention. In addition, research results anticipating the following are being obtained: the galectins retain, besides such functions, a variety of other important functions.
Galectin 9, one of tandem repeat type galectins, was first identified as an autoantigen in patients with Hodgkin's disease (Non-Patent Documents 1 & 2), and surmised to play an important role on cell-to-cell interactions among immune cells. Mouse galectin 9 was cloned from the mouse kidney cDNA library by 5′-RACE PCR with degenerated primers which were designed on the basis of sequences considered to be highly conservative among the carbohydrate recognition domains of galectins (Non-Patent Document 3). It has been found that antigen-stimulated T cells produce in vivo and in vitro an eosinophil chemoattractant, i.e., ecalectin.
Further, although ecalectin is structurally different from other eosinophil chemoattractants known up to that time, it has sugar-binding affinity to β-galactoside saccharide chains, whereby it may be classified into the galectin family. Cloning of ecalectin has been a success from mRNA obtained from human T cell-derived leukemia cell lines. As a result, it has been verified that ecalectin is one of galectin 9 variants, and galectin 9 and ecalectin are identical substances (Non-Patent Document 4).
It has been reported at present that wild type galectin 9 includes L-type galectin 9 (galectin-9 long isoform or long type galectin-9: Gal-9L), M-type galectin 9 (galectin-9 medium isoform or medium type galectin-9: Gal-9M), and S-type galectin 9 (galectin-9 short isoform or short type galectin-9: Gal-9S). Any of galectin 9 members is a molecule consisting of two carbohydrate recognition domains (CRDs) and a linker peptide that is a link region between two CRDs. L-type galectin 9 is a molecule with the longest link peptide region wherein the N-terminal domain (NCRD) is linked to the C-terminal domain (CCRD) with the aid of said link peptide region while S-type galectin 9 is a molecule with the shortest link peptide region. M-type galectin 9 is a molecule with a middle-length link peptide region as compared to both, and it has been known that Gal-9M is generally found to predominantly exist in body tissue and cells in contrast with the former two. In addition, it is perceivable that there is some evidence indicating the presence of genetic polymorphism among galectin 9 genes cloned from human cells and tissue.
Wild type galectin 9 consists of two carbohydrate recognition domains (CRDs) and a link region that is a link between said CRDs. It has been suggested that recombinant galectin 9, produced in host E. coli, induces inhibition of cancer metastasis and regression of cancers by direct actions on tumor cells (activity of inducing intercellular adhesion and apoptosis of tumor cells) and actions via the immune system. It has been revealed that galectin 9 does not act on non-activated lymphocytes while it induces apoptosis of activated lymphocytes, inter alia CD4-positive T cells which will cause hyperimmune reaction. It is also disclosed that galectin 9 has a potent apoptosis-inducing property of acting on synovial cells involved in deformity of joints or other symptoms under rheumatism.    [Non-Patent Document 1] Sahin, U. et al., Proc. Natl. Acad. Sci. USA, 92, 11810-11813 (1995)    [Non-Patent Document 2] Türeci, O. et al., J. Biol. Chem., 272(10), 6416-6422 (1997)    [Non-Patent Document 3] Wada, J. et al., J. Biol. Chem., 272(9), 6078-6086 (1997)    [Non-Patent Document 4] Matsumoto, R. et al., J. Biol. Chem., 273(27), 16976-16984 (1998)
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