Prediction and analysis of HLA-A2/A24-restricted cytotoxic T-lymphocyte epitopes of the tumor antigen MAGE-n using the artificial neural networks method on NetCTL1.2 Server

Abstract

Abstract.Cancer immunotherapy has become one of the most important therapeutic approaches to cancer in the past two decades. Tumor antigen-derived peptides have been widely used to elicit tumor-specific cytotoxic T lymphocytes (CTLs). Antigen-specific CTLs induced by MAGE-derived peptides have proven to be highly efficacious in the prevention and treatment of various types of tumor. MAGE-n is a new member of the MAGE gene family and has been shown to be closely associated with hepatocellular carcinoma. It is highly homologous to the MAGE-A gene subfamily, particularly to MAGE-3 (93%). MAGE-n-derived peptide QLVFGIEVV is a novel HLA-A2.1-restricted CTL epitope that induces MAGEn-specific CTLs in vitro. Identification of these CTL epitopes may lead to clinical applications of these peptides as cancer vaccines for patients with MAGE-n + /HLA-A2 + tumors. In the present study, HLA-A/A24-restricted CTL epitopes of antigen MAGE-n were predicted using the NetCTL1.2 Server on the web, COMB >0.85. The results showed that the NetCTL1.2 Server prediction method improved prediction efficacy and accuracy. Additionally, 8 HLA-A2-and 9 HLA-A24-restricted CTL epitope candidates (nonamers) derived from the tumor antigen MAGE-n were predicted. These nonamers, following identification via experimentation, may contribute to the development of potential antigen peptide tumor vaccines. IntroductionRecent studies have shown that tumor antigens, particularly tumor-specific antigens, which induce tumor-specific cytotoxic T lymphocytes (CTLs) and damage tumor cells, are a significant component of tumor vaccines. Epitope peptide vaccine has been of particular interest as it induces specific CTL in vitro and in vivo in order to kill target cells. Previously, a number of human genes that code for tumor antigens identified by autologous CTLs were isolated (1,2), and the epitopes derived from these tumor antigens were further identified to serve as targets for CTLs in the context of HLA class I molecules (3). MAGE-n is a newly identified member of the MAGE gene family which was first reported by our laboratory (Genebank, locus no. AF443295) (4), and was also found to be highly homologous to MAGE-A subfamily genes. Since HLA-A2/ A24 is one of the most frequently expressed molecules in the Chinese population (5,6), it is crucial to identify the tumor antigen epitopes which are presented by HLA-A2/A24 and to induce epitope-specific CTLs against tumor cells. The present study reported a simple and efficient bioinformatics method to identify candidate HLA-A2/A24-restricted CTL epitopes from the tumor antigen MAGE-n. Materials and methodsMAGE-n (316 aa) was selected as the antigen of interest in this study. The amino acid sequences of the tumor antigen were obtained from the Genbank database:Methods. HLA-A/A24-restricted CTL epitopes of antigen MAGE-n were predicted using the NetCTL1.2 Server on the web. The NetCTL1.2 Server (http://www.cbs.dtu.dk/services/ NetCTL) was used for CTL epitope prediction according to the following steps: i) input (past...

Expression of cancer–testis antigens in esophageal cancer and their progress in immunotherapy

“…First, MAGE-A, NY-ESO-1, LAGE-1, and TTK are not expressed in all esophageal cancer patients as described above; second, whether the expression of these antigens in esophageal cancer patients can trigger an effective immune response to eliminate tumor cells; third, whether there are more effective peptides for MAGE-A, NY-ESO-1, LAGE-1 and TTK that can stimulate sufficient immune responses. To solve the above problems, future research could take the expression of other members of the cancer–testis antigens family in esophageal cancer into account, considering whether there is a correlation expression among each antigen to cover more esophageal cancer patients; whether epigenetic modifying agents can effectively improve the expression of cancer–testis antigens in esophageal cancer (James et al 2006 ; Fratta et al 2011 ; Rao et al 2011 ; Kim et al 2013 ; Linnekamp et al 2017 ); using the development of computer bioinformatics technology to design the optimal peptides of MAGE-A, NY-ESO-1, LAGE-1 and TTK may significantly enhance the anti-tumor ability of CTL cells and produce ideal immune effect (Zhang et al 2010 ).…”

MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines

“…Although multiple epitopes from a single antigen have been identified and might overcome HLA restriction (i.e. MAGE-n [Zhang et al 2010], survivin [Tsuruma et al 2008; Shen et al 2013], and CEA [Nukaya et al 1999; Keogh et al 2001]), it is important that the epitopes included in such a vaccine be derived from different parent proteins. This not only will increase the clonality of the T cell response but also prevent tumor cells from downregulating a single protein and escaping the T cell response induced by the vaccine.…”

HLA-A2-Restricted Epitopes Identified from MTA1 Could Elicit Antigen-Specific Cytotoxic T Lymphocyte Response

“…Computational prediction of MTA1-derived HLA-A2-restricted CTL epitopes was conducted using online T cell epitope prediction program NetCTL1.2 [18]. Candidate peptides were synthesized using the Fmoc solid-phase strategy and then purified with the purity of >95% using reverse phase high-performance liquid chromatography (RP-HPLC) and analyzed by electrospray ionization mass spectrometry (ESI–MS).…”