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Aref AM, Hoa NT, Ge L, et al. HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma. Onco Targets Ther. 2014;7:1061-70doi: 10.2147/OTT.S61442.
Aref, A. M., Hoa, N. T., Ge, L., Agrawal, A., Dacosta-Iyer, M., Lambrecht, N., Ouyang, Y., Cornforth, A. N., & Jadus, M. R. (2014). HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma. OncoTargets and therapy, 71061-70. https://doi.org/10.2147/OTT.S61442
Aref, Ahmed M, et al. "HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma." OncoTargets and therapy vol. 7 (2014): 1061-70. doi: https://doi.org/10.2147/OTT.S61442
Aref AM, Hoa NT, Ge L, Agrawal A, Dacosta-Iyer M, Lambrecht N, Ouyang Y, Cornforth AN, Jadus MR. HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma. Onco Targets Ther. 2014 Jun 13;7:1061-70. doi: 10.2147/OTT.S61442. eCollection 2014. PMID: 24966688; PMCID: PMC4063820.
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Onco Targets Ther. 2014 Jun 13;7:1061-70. doi: 10.2147/OTT.S61442. eCollection 2014.

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

OncoTargets and therapy

Ahmed M Aref, Neil T Hoa, Lisheng Ge, Anshu Agrawal, Maria Dacosta-Iyer, Nils Lambrecht, Yi Ouyang, Andrew N Cornforth, Martin R Jadus

Affiliations

  1. 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 ; Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA, USA.
  2. Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA, USA.
  3. Department of Medicine, Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA.
  4. Pathology and Laboratory Medicine Department, Veterans Affairs Medical Center Long Beach, CA, USA ; Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
  5. California Stem Cells, Inc., CA, USA.
  6. Pathology and Laboratory Medicine Department, Veterans Affairs Medical Center Long Beach, CA, USA ; Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA ; Neuro-Oncology Program, Chao Comprehensive Cancer Center, University of California, Irvine, CA, USA.

PMID: 24966688 PMCID: PMC4063820 DOI: 10.2147/OTT.S61442

Abstract

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 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 (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.

Keywords: HCA519/TPX2; HLA‐A2; cytolytic T‐cells; tumor immunity

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