HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma.

OncoTargets and Therapy Dovepress open access to scientific and medical research Original Research Open Access Full Text Article HCA519/TPX2: a potential T-cell tumor- associated antigen for human hepatocellular carcinoma This article was published in the following Dove Press journal: OncoTargets and Therapy 13 June 2014 Number of times this article has been viewed Ahmed M Aref 1–3 Neil T Hoa 3 Lisheng Ge 3 Anshu Agrawal 4 Maria Dacosta-Iyer 5,6 Nils Lambrecht 5,6 Yi Ouyang 5,6 Andrew N Cornforth 7 Martin R Jadus 5,6,8 Biological Science Department, Modern Sciences and Arts University, Faculty of Dentistry, Cairo, Egypt; Southern California Institute for Research and Education, Veterans Affairs Medical Center, Long Beach, CA, USA; 3 Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA, USA; Department of Medicine, Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA; 5 Pathology and Laboratory Medicine Department, Veterans Affairs Medical Center Long Beach, CA, USA; 6 Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA; California Stem Cells, Inc., CA, USA; Neuro-Oncology Program, Chao Comprehensive Cancer Center, University of California, Irvine, CA, USA Correspondence: Martin R Jadus Pathology and Laboratory Medicine Department, Veterans Affairs Medical Center, Box 113, Long Beach, CA, 90822, USA Tel +1 562 826 8000 ext 4079 Email martin.jadus@va.gov Background: Immunotherapy for human hepatocellular cancer (HCC) is slowly making pro­ gress 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 precur­ sor proteins (TAPPs) messenger RNA was first screened by reverse transcriptase quantitative real-time polymerase chain reaction. Results: Four antigens (alpha fetoprotein, aspartyl/asparaginyl β-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 (HCA519 464–472 and HCA519 351–359 ) 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. Keywords: tumor immunity, cytolytic T-cells, HLA-A2, HCA519/TPX2 Introduction Hepatocellular carcinoma (HCC) is one of the most common cancers throughout the world; its increasing prevalence is due to chronic infections with hepatitis B or C viruses. 1 Treatment of established HCC with standard oncological therapies remains ineffective, and the average survival time is just several months. 2 New therapies are still desperately needed, especially those that focus on earlier biological/causative processes. Immunotherapy may be useful for future adjunct treatments of HCC. HCC takes many years, if not decades, to appear. This time provides ample oppor­ tunity to prevent the appearance of this cancer. Immunizing children with the recombi­ nant Hepatitis (HepB) virus vaccine has significantly reduced the incidence of HCC in those vaccinated people in Taiwan. 3 Although this HepB immunizing approach targets submit your manuscript | www.dovepress.com OncoTargets and Therapy 2014:7 1061–1070 Dovepress © 2014 Aref et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/OTT.S61442