Abstract
Antibody-based immunotherapy has been effectively used for tumor treatment. However, to date, only a few tumor-associated antigens (TAAs) or therapeutic targets have been identified. Identification of more immunogenic antigens is essential for improvements in multiple myeloma (MM) diagnosis and therapy. In this study, we synthesized a polyclonal antibody (PAb) by immunizing rabbits with whole human plasmacytoma ARH-77 cells and identified MM-associated antigens, including enlonase, adipophilin, and HSP90s, among others, via proteomic technologies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that 200 µg/mL PAb inhibits the proliferation of ARH-77 cells by over 50% within 48 h. Flow cytometric assay indicated that PAb treatment significantly increases the number of apoptotic cells compared with other treatments (52.1% vs. NS, 7.3% or control rabbit IgG, 9.9%). In vivo, PAb delayed tumor growth and prolonged the lifespan of mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that PAb also induces statistically significant changes in apoptosis compared with other treatments (P<0.05). We therefore conclude that PAb could be used for the effective screening and identification of TAA. PAb may have certain anti-tumor functions in vitro and in vivo. As such, its combination with proteomic technologies could be a promising approach for sieving TAA for the diagnosis and therapy of MM.
Highlights
Multiple myeloma (MM), which accounts for approximately 10% of all malignant hematologic neoplasms [1], is difficult to cure by conventional chemotherapy, high-dose radiotherapy, autologous stem cell transplantation, and allogeneic transplantation [2,3]
Our results suggest that polyclonal antibody (PAb) may be effectively used for screening and identifying tumor-associated antigens (TAAs) and that the PAb produced by the proposed method could have certain antitumor functions
Immunofluorescence and flow cytometric assay studies to detect the combination between PAb or control IgG and fixed ARH-77cells revealed that PAb significantly binds to the surface of ARH-77 but shows no reactivity to control IgG, as well as in U266 and Raji cells
Summary
Multiple myeloma (MM), which accounts for approximately 10% of all malignant hematologic neoplasms [1], is difficult to cure by conventional chemotherapy, high-dose radiotherapy, autologous stem cell transplantation, and allogeneic transplantation [2,3]. Immunotherapy based on antibodies has achieved significant success for MM treatment [4,5]. Targeting of cell-surface antigens with promising monoclonal antibodies is a very attractive approach for treating MM. Daratumumab, atlezumab, and atlizumab [5,6,7] have been evaluated in preclinical and clinical studies. Only a few tumor-associated antigens (TAAs) or therapeutic targets are currently available. Identification of novel antigens is necessary to improve MM immunotherapy
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