T-cell epitope finding on EPHA2 for further glioma vaccine development: An immunomics study.

BACKGROUND: Glioma is a deadly neurological tumor. For modern management of glioma, glioma vaccinotherapy is the new concept.
MATERIALS AND METHODS: Based on present biomedical technique, the identification of T-cell epitopes via MHC mapping can help clarify the inter-relationship of tumor and immune system. This process can be performed using advanced immunoinformatics technique.
RESULTS: Here, the author performs an immunoinformatics analysis to find alternative epitopes for glioma-related antigen, EPHA2.
CONCLUSION: After complete manipulation on EPHA2 molecules, the five best epitopes were derived.

Introduction

Glioma is a deadly neurological tumor. For modern management of glioma, glioma vaccinotherapy is the new concept. Tumor vaccine is the hope.[1] The immunomanipulation is believed to be better than classical invasive neurological approach. It is also applicable in neurological tumor. Djedid et al., mentioned that vaccinotherapy is the hope for glioma treatment.[2] New peptide-based vaccine is the aim in the present vaccine research.[3] Yang et al., said that “Preclinical animal models have shown the feasibility of an active immunotherapy approach through the utilization of tumor vaccines, and recently several clinical studies have also been initiated.”[4]

Based on present biomedical technique, the identification of T-cell epitopes via major histocompatibility complex (MHC) mapping can help clarify the inter-relationship of tumor and immune system. This process can be performed based on advanced immunoinformatics technique.[5] The clarification on the inter-relationship of tumor and immune system is the basic requirement for development of a new vaccine.[6] The use of immunoinformatics can shorten the overall period for epitopes searching. Here, the author performs an immunoinformatics analysis to find alternative epitopes for glioma-related antigen, EPHA2 based on a novel bioinformatics tool. After complete manipulation on EPHA2 molecules, the best five epitopes were derived.

Materials and Methods

In this work, potential T-cell epitopes searching on EPHA2 molecule was done using a new referenced immunoinformatics tool, created by Parker et al., which could help detect peptide binding to MHCs.[7] The protocol for this immunoinformatics research is the standard published protocol in the previous studies on cancer vaccine searchings.[8-10] The input sequence in this work was EPHA2, which was directly quoted from PubMed (www.pubmed.com). The focus is finding for the best five epitopes with the highest immunogeneticity.

Results

After manipulation on the studied molecule, EPHA2, the best five epitopes are “160TLADFDPRV”, “238SLLGLKDQV”, “202FMAAGYTAI”, “83VMWEVMTYG,” and “150KLIRAPDSL”.

Discussion

The glioma vaccine is a novel therapeutic approach for glioma treatment. There are some interesting reports from vaccine trials on animal models.[1112] Recently, some new vaccines were also tested in human beings. Ardon et al., reported a study on immunotherapy consisting of vaccination with autologous dendritic cells loaded with autologous tumor lysate and concluded that “CD127 staining is a fast, well-suited and reproducible Treg monitoring tool in HGG patients treated with immunotherapy.”[13] In addition, Sampson et al., reported their study on another new epidermal growth factor receptor variant III-targeted vaccine and found that this vaccine was safe and immunogenic in patients with glioblastoma multiforme.[14] Jian et al., concluded that “Current vaccine therapies are in clinical trials and are showing beneficial responses.”[15]

However, relevant literature does not show great benefit with the lymphocytic arm for the glioma immune regulation. This might be due to the limitation of the knowledge on this topic. Indeed, understanding on T-cell immunity can lead to the most effective therapeutic strategy to treat malignant glioma.[16] Yamanaka et al., concluded that “it may be necessary to evaluate the molecular genetic abnormalities in individual patient tumors and design novel immunotherapeutic strategies based on the pharmacogenomic findings.”[17] Nevertheless, searching for the common epitopes that can effectively induce antitumor immunity to glioma seems to be a more important process in new glioma vaccine development.[18]

Prediction of peptide binding to MHC molecules is the first step of vaccine searching. In this work, the author describes a preliminary study on glioma vaccine search. Basically, advanced computational immunomics approach via several algorithms can help assess the epitopes within the studied molecules.[7] Some recent cancer vaccine researches[8-10] also use the immunoinformatics approach for searching for primary epitopes for many oncological disorders. The multiple epitopes searching in this work can help further finding a new glioma multi-epitope vaccine. The usefulness of this technique in either cancerous[8-10] or non-cancerous disorders[19] is already approved in the previous reports.

In this work, EPHA2, which is accepted as a highlighted molecule with high possibility for using in glioma vaccine production,[20] is focused. Targeting at EPHA2 via RNA interference process is proven to result in cancer reduction.[21] Indeed, the attempt to develop EPHA2-based vaccine for glioma has been proposed for many years. In the past, when there was no advanced bioinformatics technique, the crude whole EPHA2 vaccine was studied. The quoted referenced work is the study by Hatano et al.[22] In that work,[22] success in using the vaccine for attacking melanoma is mentioned.