Abstract
Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P. This novel peptide was administered into BALB/c mice to observe the effects. Quantification of AFP-specific CD8 + T cells that secrete IFN-γ in these mice via ELISPOT revealed the synergistic effects of HSP70-P/AFP-P with increased numbers of AFP-specific CD8 + T cells. Similarly, ELISA analysis showed increased granzyme B and perforin released by natural killer cells. Moreover, in vitro cytotoxic T-lymphocyte assays and in vivo tumor preventive experiments clearly showed the higher antitumor effects of HSP70-P/AFP-P against AFP-expressing tumors. These results show that treatment of BALB/c mice with HSP70-P/AFP-P induced stronger T-cells responses and improved protective immunity. Our data suggest that HSP70-P/AFP-P may be used as a therapeutic approach in the treatment of AFP-expressing cancers.
Highlights
Cancer is one of the leading causes of deaths worldwide
Stimulation of isolated CD8 + T cells with the AFP peptide showed a significant 26-fold increase in the numbers of AFP-specific IFN-γ-secreting CD8 + T cells (478 cells/106 CD8 + T cells) only in the heat shock protein 70 (HSP70)-P/AFP-P administered mice in comparison with the three remaining control groups that received PBS, AFP-P or Heat shock proteins (HSPs)-P (17-18 cells/106 CD8 + T cells/group) (P < 0.01) (Table 2). These results suggested that HSP70 14-mer peptide TKDNNLLGRFELSG (HSP70-P)/ AFP-P vaccine elicited a strong Cytotoxic T-lymphocyte (CTL) response
These results indicated that HSP70-P/AFP-P vaccine significantly induced the response of AFP-specific natural killer cells
Summary
Among the various cancer types, hepatocellular carcinoma (HCC) accounts for about 1.2 million deaths annually [1]. This malignancy is becoming more prevalent in Asia because of the high incidences of hepatitis B and C infections [1,2]. Therapeutic vaccines can be considered for the treatment of HCC because about 80% of HCC patients express high levels of the alphafetoprotein (AFP), which can serve as a target for such immunotherapy [3,4]. A number of therapeutic approaches have been described to improve pre-existing antitumor immunity. These include recombinant plasmid DNA, chimeric virus-like www.impactjournals.com/oncotarget
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