Anti-TNFRSF17 monoclonal antibody, clone 4I7

We previously found that the haplotypes of TNFRSF17 single nucleotide polymorphisms (SNPs) were associated with the susceptibility to inflammatory bowel disease on Korean population. The present study aimed to investigate whether the polymorphisms in the TNFRSF17 gene are associated with susceptibility to colorectal cancer (CRC). Genotype analysis in the TNFRSF17 SNPs was performed by high-resolution melting and TaqMan probe analysis, and the genotype and allele frequencies of TNFRSF17 SNPs were compared between the CRC patients and the healthy controls. The haplotype frequencies of TNFRSF17 for multiple loci were estimated using the expectation maximization algorithm. Although, the genotype and allelic frequencies of these SNPs, in the colon cancer and rectal cancer patients, were not significantly different from those in the healthy controls, the genotype and allele frequency of g.2493G > A was significantly different between the healthy controls and the right colon cancer patients (P = 0.014 and 0.004, respectively). Moreover, the haplotypes frequencies in the healthy controls were significantly different from those in the colon cancer patients. Our results suggest that TNFRSF17 may be a candidate gene associated with the pathogenesis of colon cancer, and the haplotypes of the TNFRSF17 polymorphisms might be one of the markers for colon cancer susceptibility.

Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0.0157) and healthy subjects (P < 0.0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0.0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0.001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.