PMID- 24966688 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20140626 LR - 20211021 IS - 1178-6930 (Print) IS - 1178-6930 (Electronic) IS - 1178-6930 (Linking) VI - 7 DP - 2014 TI - HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma. PG - 1061-70 LID - 10.2147/OTT.S61442 [doi] AB - 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. FAU - Aref, Ahmed M AU - Aref AM AD - 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. FAU - Hoa, Neil T AU - Hoa NT AD - Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA, USA. FAU - Ge, Lisheng AU - Ge L AD - Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA, USA. FAU - Agrawal, Anshu AU - Agrawal A AD - Department of Medicine, Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA. FAU - Dacosta-Iyer, Maria AU - Dacosta-Iyer M AD - 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. FAU - Lambrecht, Nils AU - Lambrecht N AD - 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. FAU - Ouyang, Yi AU - Ouyang Y AD - 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. FAU - Cornforth, Andrew N AU - Cornforth AN AD - California Stem Cells, Inc., CA, USA. FAU - Jadus, Martin R AU - Jadus MR AD - 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. LA - eng GR - P30 CA062203/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20140613 PL - New Zealand TA - Onco Targets Ther JT - OncoTargets and therapy JID - 101514322 PMC - PMC4063820 OTO - NOTNLM OT - HCA519/TPX2 OT - HLA-A2 OT - cytolytic T-cells OT - tumor immunity EDAT- 2014/06/27 06:00 MHDA- 2014/06/27 06:01 PMCR- 2014/06/13 CRDT- 2014/06/27 06:00 PHST- 2014/06/27 06:00 [entrez] PHST- 2014/06/27 06:00 [pubmed] PHST- 2014/06/27 06:01 [medline] PHST- 2014/06/13 00:00 [pmc-release] AID - ott-7-1061 [pii] AID - 10.2147/OTT.S61442 [doi] PST - epublish SO - Onco Targets Ther. 2014 Jun 13;7:1061-70. doi: 10.2147/OTT.S61442. eCollection 2014.