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HCA519/TPX2 stimulates human CTLs - Video abstract [61442]

Video abstract of original research article HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma published in the open access journal OncoTargets and Therapy by Ahmed M Aref, Neil T Hoa, Lisheng Ge, et al. Background: Immunotherapy for human hepatocellular cancer (HCC) is slowly making progress towards treating these fatal cancers. The identification of new antigens can improve this approach. We describe a possible new antigen, hepatocellular carcinoma-associated antigen-519/targeting protein for Xklp-2 (HCA519/TPX2), for HCC that might be beneficial for T-cell specific HCC immunotherapy. Methods: HCC was studied for the expression for 15 tumor-associated antigens considered useful for immunotherapy within three HCC cell lines (HepG2, Hep3B, and PLC/PRF/5), lymphocytes, non-cancerous livers, and clinical HCC. The expression of tumor antigenic precursor proteins (TAPPs) messenger RNA was first screened by reverse transcriptase quantitative real-time polymerase chain reaction. Results: Four antigens (alpha fetoprotein, aspartyl/asparaginyl beta-hydroxylase, glypican-3 and HCA519/TPX2) proved to be the best expressed TAPPs within the HCC specimens by molecular analyses. HCA519/TPX2 was detected by intracellular cell flow cytometry within HCC cell lines by using a specific antibody towards this TAPP. This antibody also detected the protein within primary HCCs. We synthesized two HCA519/TPX2 peptides (HCA519464--472 and HCA519351--359) which can bind to human leukocyte antigen (HLA)-A*0201. Dendritic cells pulsed with these peptides stimulated cytolytic T lymphocytes (CTLs). These killer T-cells lysed HLA-A*0201+ T2 cells exogenously loaded with the correct specific peptide. The CTLs killed HepG2 (HLA-A2+ and HCA519+), but not the Hep3B and PLC/PRF/5 cell lines, which are HCA519+ but HLA-A2-negative. In silico analysis reveals that HCA519/TPX2 has the inherent ability to bind to a very wide variety of HLA antigens. Conclusion: HCA519/TPX2 is a viable immunotarget that should be further investigated within HCC patients. Read the original research paper here: http://www.dovepress.com/hca519tpx2-a-potential-t-cell-tumor-associated-antigen-for-human-hepat-peer-reviewed-article