Browsing by Author "Lambrecht N."

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    HCA519/TPX2: A potential T-cell tumor-associated antigen for human hepatocellular carcinoma
    (Dove Medical Press Ltd., 2014) Aref A.M.; Hoa N.T.; Ge L.; Agrawal A.; Dacosta-Iyer M.; Lambrecht N.; Ouyang Y.; Cornforth A.N.; Jadus M.R.; Biological Science Department; Modern Sciences and Arts University; Cairo; Egypt; Southern California Institute for Research and Education; Veterans Affairs Medical Center; Long Beach; CA; United States; Research Health Care Group; Veterans Affairs Medical Center; Long Beach; CA; United States; Department of Medicine; Division of Basic and Clinical Immunology; University of California; Irvine; CA; United States; Pathology and Laboratory Medicine Department; Veterans Affairs Medical Center Long Beach; CA; United States; Department of Pathology and Laboratory Medicine; University of California; Irvine; CA; United States; California Stem Cells; Inc; CA; United States; Chao Comprehensive Cancer Center; University of California; Irvine; CA; United States
    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 ?-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-Az.ast;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. � 2014 Aref et al. This work is published by Dove Medical Press Limited.