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ORIGINAL ARTICLE
Year : 2011  |  Volume : 6  |  Issue : 1  |  Page : 2-3
 

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


Wiwanitkit House, Bangkhae, Bangkok, India

Date of Web Publication2-Sep-2011

Correspondence Address:
Viroj Wiwanitkit
Wiwanitkit House, Bangkhae, Bangkok - 10160
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1817-1745.84398

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   Abstract 

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.


Keywords: Epitope, glioma, T cell, vaccine


How to cite this article:
Wiwanitkit V. T-cell epitope finding on EPHA2 for further glioma vaccine development: An immunomics study. J Pediatr Neurosci 2011;6:2-3

How to cite this URL:
Wiwanitkit V. T-cell epitope finding on EPHA2 for further glioma vaccine development: An immunomics study. J Pediatr Neurosci [serial online] 2011 [cited 2019 Apr 19];6:2-3. Available from: http://www.pediatricneurosciences.com/text.asp?2011/6/1/2/84398



   Introduction Top


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 Top


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],[9],[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 Top


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


   Discussion Top


The glioma vaccine is a novel therapeutic approach for glioma treatment. There are some interesting reports from vaccine trials on animal models. [11],[12] 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],[9],[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],[9],[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.

 
   References Top

1.Doherty PC, Turner SJ, Webby RG, Thomas PG. Influenza and the challenge for 52 immunology. Nat Immunol 2006;7:449-55.   Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Djedid R, Tomasi O, Haidara A, Rynkowski M, Lefranc F. Glioblastoma treatment in 2010 Rev Med Brux. 2009;30:496-505.  Back to cited text no. 2
    
3.Kanaly CW, Ding D, Heimberger AB, Sampson JH. Clinical applications of a peptide-based vaccine for glioblastoma. Neurosurg Clin N Am 2010;21:95-109.  Back to cited text no. 3
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4.Yang I, Han S, Parsa AT. Heat-shock protein vaccines as active immunotherapy against human gliomas. Expert Rev Anticancer Ther 2009;9:1577-82.  Back to cited text no. 4
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5.Braga-Neto UM, Marques ET Jr. From functional genomics to functional 56 immunomics: New challenges, old problems, big rewards. PLoS Comput Biol 2006;2:e81.  Back to cited text no. 5
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6.Parker KC, Bednarek MA, Coligan JE. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 1994;152:163-75.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.Boon AC, De Mutsert G, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF. Preferential HLA usage in the influenza virus-specific CTL response. J Immunol 2004;172:4435-43.   Back to cited text no. 7
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8.Wiwanitkit V. Intramolecular antigenicity of MUC1, a candidate for cancer vaccines. Asian Pac J Cancer Prev 2007;8:315-6.  Back to cited text no. 8
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9.Wiwanitkit V. Predicted B-cell epitopes of HER-2 oncoprotein by a bioinformatics method: A clue for breast cancer vaccine development. Asian Pac J Cancer Prev 2007;8:137-8.  Back to cited text no. 9
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10.Wiwanitkit V. Finding a T-cell epitope for a melanoma vaccine by an immunomics technique. Asian Pac J Cancer Prev 2006;7:659-60.  Back to cited text no. 10
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11.Saka M, Amano T, Kajiwara K, Yoshikawa K, Ideguchi M, Nomura S, et al. Vaccine therapy with dendritic cells transfected with Il13ra2 mRNA for glioma in mice. J Neurosurg 2010;113:270-9.  Back to cited text no. 11
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12.Ueda R, Fujita M, Zhu X, Sasaki K, Kastenhuber ER, Kohanbash G, et al. Systemic inhibition of transforming growth factor-beta in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin Cancer Res 2009;15:6551-9.  Back to cited text no. 12
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13.Ardon H, Verbinnen B, Maes W, Beez T, Van Gool S, De Vleeschouwer S. Technical advancement in regulatory T cell isolation and characterization using CD127 expression in patients with malignant glioma treated with autologous dendritic cell vaccination. J Immunol Methods 2010;352:169-73.   Back to cited text no. 13
    
14.Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Herndon JE 2 nd , Lally-Goss D, et al. An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther 2009;8:2773-9.  Back to cited text no. 14
    
15.Jian B, Yang I, Parsa AT. Monitoring immune responses after glioma vaccine immunotherapy. Neurosurg Clin N Am 2010;21:195-9.  Back to cited text no. 15
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16.Akasaki Y, Black KL, Yu JS. T cell immunity in patients with malignant glioma: Recent progress in dendritic cell-based immunotherapeutic approaches. Front Biosci 2005;10:2908-21.  Back to cited text no. 16
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17.Yamanaka R. Dendritic-cell- and peptide-based vaccination strategies for glioma. Neurosurg Rev 2009;32:265-73.  Back to cited text no. 17
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18.Yamanaka R, Itoh K. Peptide vaccination therapy for malignant glioma. Brain Nerve 2007;59:251-61.  Back to cited text no. 18
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19.Wiwanitkit V. Predicted epitopes of malarial merozoite surface protein 1 by bioinformatics method: A clue for further vaccine development. J Microbiol Immunol Infect 2009;42:19-21.  Back to cited text no. 19
[PUBMED]    
20.Hatano M, Eguchi J, Tatsumi T, Kuwashima N, Dusak JE, Kinch MS, et al. EphA2 as a glioma-associated antigen: A novel target for glioma vaccines. Neoplasia 2005;7:717-22.  Back to cited text no. 20
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21.Zhou Z, Yuan X, Li Z, Tu H, Li D, Qing J, et al. RNA interference targeting EphA2 inhibits proliferation, induces apoptosis, and cooperates with cytotoxic drugs in human glioma cells. Surg Neurol 2008;70:562-8.  Back to cited text no. 21
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22.Hatano M, Kuwashima N, Tatsumi T, Dusak JE, Nishimura F, Reilly KM, et al. Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors. J Transl Med 2004;2:40.  Back to cited text no. 22
[PUBMED]  [FULLTEXT]  




 

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    Abstract
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    Materials and Me...
   Results
   Discussion
    References

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