HCA519/TPX2: A potential T-cell tumor-associated antigen for human hepatocellular carcinoma
Aref A.M.; Hoa N.T.; Ge L.; Agrawal A.; Dacosta-Iyer M.; Lambrecht N.; Ouyang Y.; Cornforth A.N.; Jadus M.R.
Date issued:
2014
Publisher:
Dove Medical Press Ltd.
Series Info:
OncoTargets and Therapy
7
Type:
Article
Keywords:
Cytolytic T-cells
,
HCA519/TPX2
,
HLA-A2
,
Tumor immunity
,
alpha fetoprotein
,
aspartyl asparaginyl beta hydroxylase
,
glypican 3
,
HLA A antigen
,
messenger RNA
,
oxygenase
,
protein TPX2
,
tumor antigen
,
unclassified drug
,
antigen binding
,
antigen expression
,
article
,
cancer immunotherapy
,
carcinoma cell line
,
clinical article
,
computer model
,
controlled study
,
cytotoxic T lymphocyte
,
flow cytometry
,
human
,
human cell
,
liver cell carcinoma
,
protein expression
,
protein synthesis
,
real time polymerase chain reaction
,
reverse transcription polymerase chain reaction
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 ?-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.
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